1-Methylpiperazine → 9-cyclohexyl-7,7-difluoro-2-(2-methoxy-4-(4-methylpiperazine-1-carbonyl)-phenylamino)-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

HRID 1880882Notes

Reaction equation

HRID 1880882 reaction equation
[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][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.[CH3:58][N:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1>>[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([N:62]5[CH2:63][CH2:64][N:59]([CH3:58])[CH2:60][CH2:61]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 3

HCID 531671-MethylpiperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252536804-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

Product 1

HCID 579555709-cyclohexyl-7,7-difluoro-2-(2-methoxy-4-(4-methylpiperazine-1-carbonyl)-phenylamino)-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

Procedure

The title compound was synthesized from 4-(9-cyclohexyl-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 N-methylpiperazine. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27-1.35 (m, 2 H) 1.54-1.67 (m, 3 H) 1.72-1.84 (m, 5 H) 2.83 (s, 3 H) 3.31 (d, J=3.2 Hz, 3 H) 3.91 (d, J=4.6 Hz, 3 H) 3.95-4.33 (m, 10 H) 4.39-4.54 (m, 1 H) 7.06 (dd, J=8.1, 2.0 Hz, 1 H) 7.13 (d, J=110 Hz, 1 H) 8.10-8.18 (m, 1 H) 8.22 (d, J=3.0 Hz, 1 H). [M+H] calc'd for C27H35F2N7O3 544; found 544.

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

Sources & evidence

ORD record
ord-a1917b28ed5b483a85a64062784cb4f7
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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