(S)-quinuclidin-3-amine → (S)-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 914100

Reaction equation

HRID 914100 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 719216(S)-quinuclidin-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 25254154(S)-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 (S)-(−)-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 1.10-1.42 (m, 3H) 1.57-1.92 (m, 12H) 2.71-89 (m, 4H) 2.96 (m, 1H) 3.13 (m, 1H) 3.31 (s, 3H) 3.95 (s, 3H) 3.97-4.10 (m, 2H) 4.45 (m, 1H) 7.47 (d, J=8.0 Hz, 1H) 7.50 (s, 1H) 7.93 (s, 1H) 8.19 (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-0081ee5375a545b0a518a5bd7a7f61b2
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Linked notes

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