Trifluoroacetic acid methylene chloride → 6-Phenethyl-7-(trifluoromethyl)-1,2,3,4,6,7-hexahydro-[1,4]diazepino[6,7,1-hi]indol-6-ol trifluoroacetate
Reaction equation
O[C:2]1([C:30]([F:33])([F:32])[F:31])[CH:10]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]=[C:8]2[CH2:19][NH:20][CH:21](C(OC(C)(C)C)=O)[CH2:22][N:6]3[C:7]2=[C:3]1[CH:4]=[CH:5]3.C(Cl)Cl.[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40]>>[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40].[CH2:11]([C:10]1([OH:40])[CH:9]=[C:8]2[CH2:19][NH:20][CH2:21][CH2:22][N:6]3[C:7]2=[C:3]([CH:4]=[CH:5]3)[CH:2]1[C:30]([F:31])([F:32])[F:33])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1Participants
Reactant 2
Product 1
Procedure
The Boc group was removed from tert-butyl 7-hydroxy-6-phenethyl-7-(trifluoromethyl)-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indole-2(1H)-carboxylate (138 mg, 0.3 mmol) (prepared as in Example 2 above) under standard conditions (CH2Cl2/trifluoroacetic acid) yielded 6-phenethyl-7-(trifluoromethyl)-1,2,3,4,6,7-hexahydro-[1,4]diazepino[6,7,1-hi]indol-6-ol trifluoroacetate, which was dissolved in THF (5 mL) and the resulting mixture was cooled to 0° C. Triethylamine (3.75 eq) was added, followed by addition of isopropyl isocyanate (1.7 eq). The resulting mixture was stirred at 0° C. for 30 min, then warmed to room temperature and stirred overnight. The resulting mixture was concentrated, dissolved in ethyl acetate (20 mL), and washed sequentially with water, NaHCO3 (sat. aq.) and brine, then dried (Na2SO4) and concentrated to yield 7-hydroxy-N-isopropyl-6-phenethyl-7-(trifluoromethyl)-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indole-2(1H)-carboxamide (134 mg, MH+=448).
Sources & evidence
- ORD record
- ord-d45b5c9d3c8a4e6daf7456cc837ec987
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216998B2
Reaction notes
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