(7S)-4-chloro-9-(2,2-dimethylpropyl)-7-[2-oxo-2-[4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidin-1-yl]ethyl]-3,6,7,10-tetrahydropyrazolo[3,4-i][2]benzazepin-8-one → (S)-4-Chloro-7-(2-(4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidin-1-yl)-2-oxoethyl)-9-(pyridin-4-ylmethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one

HRID 132482Notes

Reaction equation

HRID 132482 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:12]2[NH:11][N:10]=[CH:9][C:8]=2[C:7]2[CH2:13][N:14]([CH2:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[C:15](=[O:22])[C@H:16]([CH2:18][C:19](O)=[O:20])[CH2:17][C:6]=2[CH:5]=1.Cl.[F:31][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:41]=1[NH:40][C:39](=[O:42])[N:38]([CH:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)[CH2:37]2.ClC1C2NN=CC=2C2CN(CC(C)(C)C)C(=O)[C@H](CC(=O)N3CCC(N4CC5C(=CC=CC=5)NC4=O)CC3)CC=2C=1>>[Cl:3][C:4]1[C:12]2[NH:11][N:10]=[CH:9][C:8]=2[C:7]2[CH2:13][N:14]([CH2:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)[C:15](=[O:22])[C@H:16]([CH2:18][C:19]([N:46]3[CH2:45][CH2:44][CH:43]([N:38]4[CH2:37][C:36]5[C:41](=[C:32]([F:31])[CH:33]=[CH:34][CH:35]=5)[NH:40][C:39]4=[O:42])[CH2:48][CH2:47]3)=[O:20])[CH2:17][C:6]=2[CH:5]=1

Participants

4

Reactant 3

HCID 11979011(7S)-4-chloro-9-(2,2-dimethylpropyl)-7-[2-oxo-2-[4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidin-1-yl]ethyl]-3,6,7,10-tetrahydropyrazolo[3,4-i][2]benzazepin-8-oneHCID 67202381(S)-2-(4-Chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid dihydrochlorideHCID 688256668-fluoro-3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one hydrochloride

Product 1

HCID 11979245(S)-4-Chloro-7-(2-(4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidin-1-yl)-2-oxoethyl)-9-(pyridin-4-ylmethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-oneYield 16%

Procedure

(S)-2-(4-Chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid dihydrochloride (100 mg, 0.2 mmol) and 8-fluoro-3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one hydrochloride (61 mg, 0.2 mmol) were reacted in a manner analogous to the preparation of 4-Chloro-9-(2,2-dimethyl-propyl)-7-(S)-{2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-ethyl}-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one. Title compound was obtained as white solid in 16% yield. MS m/e (M+H)+=616.2. 1H NMR (500 MHz, DMSO-D6): δ=13.46 (s, 1H), 9.23 (d, J=6.41, 1H), 8.31 (m, 2H), 8.24 (d, J=6.10, 1H), 7.22 (s, 1H), 7.13 (dd, J1=9.46, J2=4.88, 2H), 7.05 (m, 1H), 6.91 (m, 1H), 6.85 (s, 1H), 5.40 (d, J=17.09, 1H), 4.66 (m, 3H), 4.54 (d, J=11.90, 1H), 4.41 (m, 1H), 4.36 (s, 1H), 4.28 (d, J=4.58 1H), 4.10 (d, J=12.51, 1H), 4.00 (m, 1H), 3.17 (m, 2H), 3.04 (m, 1H), 2.94 (m, 1H), 2.62 (d, J=11.29, 1H), 2.43 (m, 1H), 1.83 (m, 1H), 1.62 (m, 3H).

Sources & evidence

ORD record
ord-224f446cea1d4e3789484c6f4260f3ba
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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