3-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one → (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidine-1-carboxylate

HRID 2378997Notes

Reaction equation

HRID 2378997 reaction equation
[C:1](=[O:34])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][C@H:3]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([F:23])([F:22])[F:21])[CH2:15][C:6]2[C:7]3[CH:8]=[N:9][NH:10][C:11]=3[C:12]([Cl:14])=[CH:13][C:5]=2[CH2:4]1.[NH:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:47][CH2:46][C:45]3[CH:48]=[CH:49][CH:50]=[CH:51][C:44]=3[NH:43][C:42]2=[O:52])[CH2:37][CH2:36]1>ClCCl>[O:52]=[C:42]1[NH:43][C:44]2[CH:51]=[CH:50][CH:49]=[CH:48][C:45]=2[CH2:46][CH2:47][N:41]1[CH:38]1[CH2:39][CH2:40][N:35]([C:1]([O:2][C@H:3]2[C:17](=[O:18])[N:16]([CH2:19][C:20]([F:23])([F:22])[F:21])[CH2:15][C:6]3[C:7]4[CH:8]=[N:9][NH:10][C:11]=4[C:12]([Cl:14])=[CH:13][C:5]=3[CH2:4]2)=[O:34])[CH2:36][CH2:37]1

Participants

4

Reactant 2

HCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 59732082(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl 4-nitrophenyl carbonate

Product 1

HCID 59006340(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl 4-nitrophenyl carbonate (60 mg, 0.120 mmol) in dichloromethane (15 mL) was added 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (32.5 mg, 0.132 mmol). The reaction mixture was stirred for 2 h. LC-MS analysis suggested formation of product (Rf=2.473, 605.22 (M+H)). The reaction mixture was washed with aqueous NaHCO3 followed by 1.0 M HCl. THe crude product was purified by flash chromatography using 5% MeOH in dichloromethane to give (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidine-1-carboxylate (29.00 mg, 0.048 mmol, 40% yield). 1H NMR (500 MHz, CD3OD): in δ 8.30 (s, 1H), 7.32 (s, 1H), 7.09 (m, 3H), 6.93-6.87 (m, 3H), 6.09-6.05 (m, 1H), 5.50 (s, 2H), 5.44 (m, 1H), 4.68-4.54 (m, 1H), 4.39-4.35 (m, 2H), 4.32-4.19 (m, 1H), 4.16-4.05 (m, 3H), 3.55-3.50 (m, 3H), 3.12-2.92 (m, 2H), 1.87-1.74 (m, 4H); MS (ESI) 605 (M+H); Rf=2.47.

Workup

  1. washThe reaction mixture was washed with aqueous NaHCO3
  2. customTHe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-979dc93b171c495bb72f277f9da8a498
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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