Hydrazine hydrate (1:1) → 4-Trifluoromethylphenyl-[1,2]diazepino[4,5,6-cd]indol-6-one

HRID 33347Notes

Reaction equation

HRID 33347 reaction equation
C1([C:7]2[C:13]3=[CH:14][NH:15][C:16]4[CH:17]=[CH:18][CH:19]=[C:11]([C:12]=43)[C:10](=[O:20])[NH:9][N:8]=2)C=CC=CC=1.N1C2C=CC=C(C(OC)=O)C=2C=C1.[F:34][C:35]([F:46])([F:45])[C:36]1[CH:44]=[CH:43][C:39](C(Cl)=O)=[CH:38][CH:37]=1.[Cl-].[Al+3].[Cl-].[Cl-].O.NN>ClC(Cl)C.CO.Cl>[F:34][C:35]([F:46])([F:45])[C:36]1[CH:44]=[CH:43][C:39]([C:14]2[C:13]3=[CH:7][N:8]=[N:9][C:10](=[O:20])[C:11]4[C:12]3=[C:16]([CH:17]=[CH:18][CH:19]=4)[N:15]=2)=[CH:38][CH:37]=1

Participants

9

Reactant 5

HCID 24654Hydrazine hydrate (1:1)HCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 2733668methyl 1H-indole-4-carboxylateHCID 6451240Aluminum(III) ChlorideHCID 1354630341,5-Dihydro-3-phenyl-[1,2]diazepino[4,5,6-cd]-indol-6-one

Product 1

HCID 865877074-Trifluoromethylphenyl-[1,2]diazepino[4,5,6-cd]indol-6-one

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Procedure

In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (250 mg, 1.43 mmol) in dichloroethane (3 mL) was treated with p-trifluoromethylbenzoyl chloride (445 mg, 2.14 mmol) and aluminum chloride (572 mg). The intermediate ketone (95 mg, 0.27 mmol) in MeOH (3 mL) and conc. HCl (0.05 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with w M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/hexanes) to give 1,5-dihydro-3-(4-trifluoromethylphenyl-[1,2]diazepino[4,5,6-cd]indol-6-one, 30 mg (34%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.24 (app br t, 1H), 7.29 (d, J=2.8 Hz, 2H), 7.60 (m, 2H), 7.82 (m, 4H), 10.57 (s, 1H), 12.01 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668.

Workup

  1. customThe reaction was quenched at 0° C. with w M NaOAc
  2. customThe product was isolated by extraction with CH2Cl2
  3. customrecrystallized (CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-a70c0399768a4671821172362cf6c4f3
Source dataset
uspto-grants-2008_09
Patent number
US07429578B2

Reaction notes

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