公开(公告)号：US12049453B2

公开(公告)日：2024-07-30

申请号：US17826449

申请日：2022-05-27

申请人： MannKind Corporation

发明人： John J. Freeman ,  Otto Phanstiel ,  William Elliot Bay ,  Kelly Sullivan Kraft

IPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

CPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

摘要： A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

公开(公告)号：US11345668B2

公开(公告)日：2022-05-31

申请号：US17130729

申请日：2020-12-22

申请人： MannKind Corporation

发明人： John J. Freeman ,  Otto Phanstiel ,  William Elliot Bay ,  Kelly Sullivan Kraft

IPC分类号： C07D241/08 ,  C07D241/10 ,  C07D241/04

摘要： A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

公开(公告)号：US20210114994A1

公开(公告)日：2021-04-22

申请号：US17113540

申请日：2020-12-07

申请人： MannKind Corporation

发明人： Kelly Sullivan Kraft ,  John J. Freeman ,  Paul Serwinski ,  Vincent Pavia ,  Otto Phanstiel ,  Navneet Kaur

IPC分类号： C07D241/08 ,  C07C201/12 ,  C07C67/39 ,  C07C67/30

摘要： Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

公开(公告)号：US09944609B2

公开(公告)日：2018-04-17

申请号：US14942410

申请日：2015-11-16

申请人： MannKind Corporation

发明人： John J. Freeman ,  Otto Phanstiel ,  William Elliot Bay ,  Kelly Sullivan Kraft

IPC分类号： C07D241/08 ,  C07D241/10 ,  C07D241/04

CPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

摘要： A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

公开(公告)号：US20160159753A1

公开(公告)日：2016-06-09

申请号：US14949489

申请日：2015-11-23

申请人： MannKind Corporation

发明人： Kelly Sullivan Kraft ,  John J. Freeman ,  Paul Serwinski ,  Vincent Pavia ,  Otto Phansteil ,  Navneet Kaur

IPC分类号： C07D241/08

CPC分类号： C07D241/08 ,  C07C67/30 ,  C07C67/39 ,  C07C201/12 ,  C07C69/60 ,  C07C205/43

摘要： Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

摘要翻译： 公开的实施方案涉及用于合成活化的富马酸盐中间体的改进方法及其在化学合成中的用途。 公开的实施方案描述了活化的富马酸酯的合成，包括衍生自活化基团的活化的富马酸酯，包括：4-硝基苯基，二苯基磷酰叠氮化物，新戊酰氯，氯磺酰异氰酸酯，对硝基苯酚，MEF，三氟乙酰基和氯，例如乙基富马酰氯， 的活性酯原位。 另外的实施方案描述了从单分离和未纯化的中间体改进的取代氨基烷基 - 二酮哌嗪的合成，其允许提高产率和反应器生产量。

公开(公告)号：US11479535B2

公开(公告)日：2022-10-25

申请号：US17113540

申请日：2020-12-07

申请人： MannKind Corporation

发明人： Kelly Sullivan Kraft ,  John J. Freeman ,  Paul Serwinski ,  Vincent Pavia ,  Otto Phanstiel ,  Navneet Kaur

IPC分类号： C07D241/08 ,  C07C201/12 ,  C07C67/39 ,  C07C67/30

摘要： Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

公开(公告)号：US20180230107A1

公开(公告)日：2018-08-16

申请号：US15953817

申请日：2018-04-16

申请人： MannKind Corporation

发明人： John J. Freeman ,  Otto Phanstiel ,  William Elliot Bay ,  Kelly Sullivan Kraft

IPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

CPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

摘要： A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

公开(公告)号：US20160137614A1

公开(公告)日：2016-05-19

申请号：US14942410

申请日：2015-11-16

申请人： MannKind Corporation

发明人： John J. Freeman ,  Otto Phanstiel ,  William Elliot Bay ,  Kelly Sullivan Kraft

IPC分类号： C07D241/08

CPC分类号： C07D241/08 ,  C07D241/04 ,  C07D241/10

摘要： A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

公开(公告)号：US20240180897A1

公开(公告)日：2024-06-06

申请号：US18437733

申请日：2024-02-09

申请人： MannKind Corporation

发明人： John J. Freeman ,  Marshall L. Grant ,  Jason J. Antunovich ,  William Elliott Bay

IPC分类号： A61K31/495 ,  A61K9/00 ,  A61K31/191 ,  A61P9/12

CPC分类号： A61K31/495 ,  A61K9/0075 ,  A61K31/191 ,  A61P9/12

摘要： Inhalable compositions for treating pulmonary hypertension comprising treprostinil, derivative thereof or analogs thereof and a method for treating pulmonary arterial hypertension and/or idiopathic pulmonary fibrosis are disclosed herein. Methods of manufacturing pharmaceutical compositions are also disclosed. Compositions are based on diketopiperazine powders for pulmonary inhalation.

公开(公告)号：US10858325B2

公开(公告)日：2020-12-08

申请号：US16126323

申请日：2018-09-10

申请人： MannKind Corporation

发明人： Kelly Sullivan Kraft ,  John J. Freeman ,  Paul Serwinski ,  Vincent Pavia ,  Otto Phanstiel ,  Navneet Kaur

IPC分类号： C07D241/06 ,  C07D241/08 ,  C07C201/12 ,  C07C67/39 ,  C07C67/30

摘要： Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.