4-Amino-1-Boc-piperidine → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(piperidin-4-yl)benzamide

HRID 914063

Reaction equation

HRID 914063 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][CH:58]1[CH2:63][CH2:62][N:61](C(OC(C)(C)C)=O)[CH2:60][CH2:59]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:57][CH:58]5[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 252530654-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(piperidin-4-yl)benzamide

Procedure

The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and tert-butyl 4-aminopiperidine-1-carboxylate, where Boc was removed using TFA in DCM. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (qd, J=11.9, 3.8 Hz, 2H) 1.54-1.66 (m, 5H) 1.66-1.77 (m, 4H) 1.98 (br. s, 2H) 2.52 (d, J=1.8 Hz, 2H) 2.98 (d, J=11.9 Hz, 2H) 3.79-3.87 (m, 1H) 3.93 (s, 3H) 4.04 (t, J=14.2 Hz, 2H) 4.76 (quin, J=8.1 Hz, 1H) 7.48 (d, 1H) 7.50 (s, 1H) 7.96 (s, 1H) 8.13 (d, J=8.1 Hz, 1H) 8.26 (d, J=8.1 Hz, 1H) 8.26 (s, 1H). [M+H] calc'd for C26H33F2N7O3, 530. found 530.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. customwas removed
  3. customThe final compound was purified by reverse phase HPLC
  4. customto give the free base

Sources & evidence

ORD record
ord-80ce3d06b4724fa2990e25473b1747ef
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Linked notes

Loading…