N,N-Dimethyl-1,4-cyclohexanediamine → 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(4-(dimethylamino)cyclohexyl)-3-methoxybenzamide

HRID 1880874Notes

Reaction equation

HRID 1880874 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](O)=[O:28])=[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]([CH3:67])[CH:60]1[CH2:65][CH2:64][CH:63]([NH2:66])[CH2:62][CH2:61]1>>[CH:1]1([N:7]2[CH2:13][C:12]([F:14])([F:15])[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]([NH:66][CH:63]5[CH2:64][CH2:65][CH:60]([N:59]([CH3:67])[CH3:58])[CH2:61][CH2:62]5)=[O:28])=[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

Participants

4

Reactant 3

HCID 345823N,N-Dimethyl-1,4-cyclohexanediamineHCID 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 252541584-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(4-(dimethylamino)cyclohexyl)-3-methoxybenzamide

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 N1,N1-dimethylcyclohexane 1,4-diamine. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11-1.96 (m, 18 H) 2.17 (s, 6 H) 3.31 (s, 3 H) 3.73 (m, 1 H) 3.92 9m, 1 H) 3.94 (s, 3 H) 4.06 (t, J=13.52 Hz, 2 H) 4.46 (m, 1 H) 7.42-7.59 (m, 2 H) 7.89 (s, 1 H) 8.11 (m, 1 H) 8.21 (s, 1 H) 8.26 (d, J=8.34 Hz, 1 H). Melting point: 208-214° C. [M+H] calculated for C30H41F2N7O3, 586; found 586.

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-ffcbeee75f5d449db177b5fcc276c4ad
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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