Dichloromethane → (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

HRID 132448Notes

Reaction equation

HRID 132448 reaction equation
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:13](=[O:17])[C@H:14]([OH:16])[CH2:15][C:4]=2[CH:3]=1.ClCCl.C(N(C(C)C)CC)(C)C.[C:35](Cl)(=[O:46])[O:36][C:37]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=1>>[C:35](=[O:46])([O:36][C:37]1[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=1)[O:16][C@H:14]1[C:13](=[O:17])[N:12]([CH2:18][C:19]([F:21])([F:20])[F:22])[CH2:11][C:5]2[C:6]3[CH:7]=[N:8][NH:9][C:10]=3[C:2]([Cl:1])=[CH:3][C:4]=2[CH2:15]1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 59732071HCID 59732071, compound

Product 1

HCID 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 carbonateYield 56%

Procedure

(R)-4-chloro-7-hydroxy-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (1.2 g, 3.60 mmol) in dichloromethane (100.0 ml, 1554 mmol) was added diisopropylethyl amine (0.651 g, 5.03 mmol) followed by 4-nitrophenyl carbonochloridate (0.942 g, 4.67 mmol). After 48 h, the reaction mixture was washed with 1.0 M HCl and the crude product was purified by flash chromatography using 75% EtOAc in hexane 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-nitrophenyl carbonate (1.0 g, 2.005 mmol, 56% yield). MS (ESI) 499 (M+H) ; Rf=1.64.

Workup

  1. washthe reaction mixture was washed with 1.0 M HCl
  2. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-e30272791a7d4c4ea11e97c59b3a195c
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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