4-Amino-1-methylpiperidine → 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-fluoro-N-(1-methylpiperidin-4-yl)benzamide

HRID 1880847

Reaction equation

HRID 1880847 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[F:31])=[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.[CH3:56][N:57]1[CH2:62][CH2:61][CH:60]([NH2:63])[CH2:59][CH2:58]1>>[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]([NH:63][CH:60]5[CH2:61][CH2:62][N:57]([CH3:56])[CH2:58][CH2:59]5)=[O:27])=[CH:24][C:23]=4[F:31])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 3

HCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 580150834-(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-fluoro-benzoic acid

Product 1

HCID 252533734-(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-fluoro-N-(1-methylpiperidin-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[4,5-b][1,4]diazepin-2-ylamino)-3-fluorobenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-methylpiperidin-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50-1.75 (m, 12 H) 1.99 (m, 3 H) 2.19 (s, 3 H) 2.79 (m, 2 H) 3.74 (m, 1 H) 4.01 (t, J=14.0 Hz, 2 H) 4.68 (m, 1 H) 7.67 (d, J=8.6 Hz, 1 H) 7.72 (d, J=12.4 Hz, 1 H) 7.99 (t, J=8.2 Hz, 1 H) 8.20 (d, J=7.3 Hz, 1 H) 8.23 (s, 1 H) 9.08 (s, 1 H). [M+H] calc'd for C26H32F3N7O2, 532; found 532.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. customThe final compound was purified by reverse phase HPLC
  3. customto give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50-1.75 (m, 12 H) 1.99 (m, 3 H) 2.19 (s, 3 H) 2.79 (m, 2 H) 3.74 (m, 1 H) 4.01 (t, J=14.0 Hz, 2 H) 4.68 (m, 1 H) 7.67 (d, J=8.6 Hz, 1 H) 7.72 (d, J=12.4 Hz, 1 H) 7.99 (t, J=8.2 Hz, 1 H) 8.20 (d, J=7.3 Hz, 1 H) 8.23 (s, 1 H) 9.08 (s, 1 H)

Sources & evidence

ORD record
ord-de01ea094bf44b0cb179a61bd02391c4
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Linked notes

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