Triethylamine → 4,4,4-trifluoro-3-methyl-1-(6-phenethyl-7-(trifluoromethyl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-2(1H)-yl)butan-1-one

HRID 1505732Notes

Reaction equation

HRID 1505732 reaction equation
[CH2:1]([C:9]1[C:10]([C:22]([F:25])([F:24])[F:23])=[C:11]2[C:15]3=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:14]3[CH:13]=[CH:12]2)[CH:17]=1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[F:26][C:27]([F:35])([F:34])[CH:28]([CH3:33])[CH2:29][C:30](O)=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C1COCC1>[F:26][C:27]([F:35])([F:34])[CH:28]([CH3:33])[CH2:29][C:30]([CH:20]1[NH:19][CH2:18][C:16]2=[C:15]3[C:11](=[C:10]([C:22]([F:25])([F:24])[F:23])[C:9]([CH2:1][CH2:2][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[CH:17]2)[CH:12]=[CH:13][N:14]3[CH2:21]1)=[O:31]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1361744,4,4-Trifluoro-3-methylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866919886-Phenethyl-7-(trifluoromethyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indole

Product 1

HCID 866920034,4,4-trifluoro-3-methyl-1-(6-phenethyl-7-(trifluoromethyl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-2(1H)-yl)butan-1-oneYield 95.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-phenethyl-7-(trifluoromethyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indole (prepared as described in Example 2 above, 64 mg, 0.17 mmol), 3-(trifluoromethyl)butanoic acid (27 mg, 0.18 mmol), HATU (73 mg, 0.2 mmol) and triethylamine (85 mg, 0.84 mmol) in THF (7 mL) was stirred overnight. The resulting mixture was partitioned between ethyl acetate and water, and the organic layer was washed sequentially with NaHCO3 (sat'd) and brine, then dried and concentrated. The residue was purified by reverse-phase chromatography (CH3CN-water/TFA) to yield 4,4,4-trifluoro-3-methyl-1-(6-phenethyl-7-(trifluoromethyl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-2(1H)-yl)butan-1-one (78 mg).

Workup

  1. customThe resulting mixture was partitioned between ethyl acetate and water
  2. washthe organic layer was washed sequentially with NaHCO3 (sat'd) and brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by reverse-phase chromatography (CH3CN-water/TFA)

Sources & evidence

ORD record
ord-a822854cf32843fcae90bdb572a606ad
Source dataset
uspto-grants-2015_12
Patent number
US09216998B2

Reaction notes

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