(3R)-1-Azabicyclo(2.2.2)octan-3-amine → (R)-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-(quinuclidin-3-yl)benzamide

HRID 914099

Reaction equation

HRID 914099 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.[NH2:58][C@@H:59]1[CH:64]2[CH2:65][CH2:66][N:61]([CH2:62][CH2:63]2)[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]([NH:58][C@@H:59]5[CH:64]6[CH2:65][CH2:66][N:61]([CH2:62][CH2:63]6)[CH2:60]5)=[O:29])=[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 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 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 25254155(R)-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-(quinuclidin-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 (R)-(+)-3-aminoquinuclidine. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-1.43 (m, 3H) 1.57-1.92 (m, 12H) 2.69 (d, J=6.57 Hz, 2H) 2.71 (m, 3H) 2.89 (m, 1H) 3.13 (m, 1H) 3.31 (s, 3H) 3.95 (s, 3H) 3.97-4.16 (m, 2H) 4.45 (m, 1H) 7.47 (d, J=8.0 Hz, 1H) 7.49 (s, 1H) 7.93 (s, 1H) 8.14 (d, 1H) 8.21 (s, 1H) 8.26 (d, J=8.0 Hz, 1H). [M+H] calculated for C29H37F2N7O3, 570. found 570.

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-1fc8332e772f47d1bf6e85c68b42751c
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Linked notes

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