Ammonia → 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide

HRID 2238382Notes

Reaction equation

HRID 2238382 reaction equation
[NH3:1].[Cl:2][CH2:3][CH:4]1[C:12]2[C:11]3[CH:13]=[CH:14][C:15]([S:17](Cl)(=[O:19])=[O:18])=[CH:16][C:10]=3[C:9]([N+:21]([O-:23])=[O:22])=[CH:8][C:7]=2[N:6]([C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH2:5]1.O.Cl>C1COCC1.[Cl-].[Na+].O.CCOC(C)=O>[Cl:2][CH2:3][CH:4]1[C:12]2[C:11]3[CH:13]=[CH:14][C:15]([S:17]([NH2:1])(=[O:19])=[O:18])=[CH:16][C:10]=3[C:9]([N+:21]([O-:23])=[O:22])=[CH:8][C:7]=2[N:6]([C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH2:5]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 962WaterHCID 866202591-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonyl chloride

Product 1

HCID 445509951-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonamideYield 77%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Conc. aqueous NH3 (0, 32 mL, 4.7 mmol) was added to a solution of 116 (215 mg, 0.47 mmol) in THF (10 mL) at −78° C. After 10 min water (10 mL), aqueous HCl (2 N, 5 mL, 9.4 mmol), and EtOAc (20 mL) were added and the mixture was allowed to warm to room temperature. Brine was added and the mixture was extracted with EtOAc (×2). The combined extracts were washed with brine and dried, and the EtOAc solution was evaporated onto silica. Chromatography eluting with EtOAc/petroleum ether (1:10 then 1:3 then 2:1) gave 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide (123) (158 mg, 77%) as a pale yellow solid: mp (EtOAc) 274-278° C. (dec.); 1H NMR [(CD3)2SO] δ 9.11 (s, 1H), 8.89 (d, J=1.6 Hz, 1H), 8.50 (d, J=8.9 Hz, 1H), 8.11 (dd, J=8.9, 1.7 Hz, 1H), 7.66 (s, 1H), 4.73-4.64 (m, 2H), 4.57-4.49 (m, 1H), 4.24-4.11 (m, 2H). Anal. (C15H11ClF3N3O5S) C, H, N.

Workup

  1. extractionthe mixture was extracted with EtOAc (×2)
  2. washThe combined extracts were washed with brine
  3. customdried
  4. customthe EtOAc solution was evaporated onto silica
  5. washChromatography eluting with EtOAc/petroleum ether (1:10

Sources & evidence

ORD record
ord-45c370250d764c379188bfb344790942
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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