8-methyl-8-azabicyclo[3.2.1]octan-3-amine Dihydrochloride → 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)-3-methoxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)benzamide

HRID 1880876Notes

Reaction equation

HRID 1880876 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.Cl.Cl.[CH3:60][N:61]1[CH:66]2[CH2:67][CH2:68][CH:62]1[CH2:63][CH:64]([NH2:69])[CH2:65]2>>[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:69][CH:64]5[CH2:65][CH:66]6[N:61]([CH3:60])[CH:62]([CH2:68][CH2:67]6)[CH2:63]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 27759288-methyl-8-azabicyclo[3.2.1]octan-3-amine DihydrochlorideHCID 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 252543054-(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-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)benzamide

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 8-methyl-8-azabicyclo[3.2.1]octan-3-amine dihydrochloride. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13-1.45 (m, 4 H) 1.37-1.85 (m, 12 H) 1.99 (s, 2 H) 2.29 (br. s., 2 H) 3.31 (s, 3 H) 3.93 (s, 3 H) 3.97-4.22 (m, 3 H) 4.45 (m, 1 H) 7.47 (d, J=8.0 Hz, 1 H) 7.49 (s, 1 H) 7.90 (s, 1 H) 8.15 (d, 1 H) 8.20 (s, 1 H) 8.25 (d, J=8.34 Hz, 1 H). [M+H] calculated for C30H39F2N7O3, 584; found 584.

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-5606ce74bcbb4145adb340b97b2ec8f3
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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