Hydrazine hydrate (1:1) → 1,5-Dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one

HRID 489571Notes

Reaction equation

HRID 489571 reaction equation
C1(C2[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:43])([C:39]([F:42])([F:41])[F:40])[C:36](Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-].O.NN>ClC(Cl)C.CO.Cl>[F:34][C:35]([F:43])([C:36]1[C:13]2=[CH:14][NH:15][C:16]3[CH:17]=[CH:18][CH:19]=[C:11]([C:12]=32)[C:10](=[O:20])[NH:9][N:8]=1)[C:39]([F:42])([F:41])[F:40]

Participants

9

Reactant 5

HCID 24654Hydrazine hydrate (1:1)HCID 67911Perfluoropropionyl 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 1355841841,5-Dihydro-3-pentafluoroethyl-[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 (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 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/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668.

Workup

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

Sources & evidence

ORD record
ord-f3997a6967ca48e8839f7de9ac6390c3
Source dataset
uspto-grants-2005_12
Patent number
US06977298B2

Reaction notes

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