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 914076

Reaction equation

HRID 914076 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, 12H) 1.99 (m, 3H) 2.19 (s, 3H) 2.79 (m, 2H) 3.74 (m, 1H) 4.01 (t, J=14.0 Hz, 2H) 4.68 (m, 1H) 7.67 (d, J=8.6 Hz, 1H) 7.72 (d, J=12.4 Hz, 1H) 7.99 (t, J=8.2 Hz, 1H) 8.20 (d, J=7.3 Hz, 1H) 8.23 (s, 1H) 9.08 (s, 1H). [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, 12H) 1.99 (m, 3H) 2.19 (s, 3H) 2.79 (m, 2H) 3.74 (m, 1H) 4.01 (t, J=14.0 Hz, 2H) 4.68 (m, 1H) 7.67 (d, J=8.6 Hz, 1H) 7.72 (d, J=12.4 Hz, 1H) 7.99 (t, J=8.2 Hz, 1H) 8.20 (d, J=7.3 Hz, 1H) 8.23 (s, 1H) 9.08 (s, 1H)

Sources & evidence

ORD record
ord-714a548836f640c7b588e8f5ddce1a20
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Linked notes

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