4-Methylmorpholine → N-(4-fluoro-benzyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamide

HRID 737046Notes

Reaction equation

HRID 737046 reaction equation
[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([S:16]([C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.[F:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40][NH2:41])=[CH:38][CH:37]=1>C1COCC1>[F:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40][NH:41][C:23](=[O:24])[C:22]2[CH:26]=[CH:27][C:19]([S:16]([N:9]3[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[CH:8]3)(=[O:17])=[O:18])=[CH:20][CH:21]=2)=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 673264-FluorobenzylamineHCID 589751414-(3-Phenyl-indole-1-sulfonyl)-benzoic acid

Product 1

HCID 11465854N-(4-fluoro-benzyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamideYield 75.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a 100 ml RBF combine 4-(3-phenyl-indole-1-sulfonyl)-benzoic acid (2.5 g, 6.62 mmol) and THF (25 ml). Cool the solution in an ice water bath and add 4-methylmorpholine (0.73 ml, 7.29 mmol) follow by the portion wise addition of CDMT (1.16 g, 7.29 mmol). Stir the solution in an ice water bath for one hour. Add dropwise, a solution of 4-fluorobenzylamine (0.83 ml, 7.29 mmol) in THF (8 μl) to the reaction at 0° C. Stir the solution at 0° C. for five hours, and quench with 1N HCl (50 ml). Extract the reaction MTBE (2×50 ml), filter and wash with saturated aqueous sodium chloride (50 ml). Dry the organics over magnesium sulfate, filter and concentrate to give N-(4-fluoro-benzyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamide (2.43 g) as a white solid. HPLC=95.5%, MS (ESI) m/z observed 485.1334 calculated 485.1335 (M+H).

Workup

  1. temperatureCool the solution in an ice water bath
  2. additionfollow by the portion wise addition of CDMT (1.16 g, 7.29 mmol)
  3. additionAdd dropwise
  4. stirringStir the solution at 0° C. for five hours
  5. customquench with 1N HCl (50 ml)
  6. extractionExtract
  7. customthe reaction MTBE (2×50 ml)
  8. filtrationfilter
  9. washwash with saturated aqueous sodium chloride (50 ml)
  10. dry with materialDry the organics over magnesium sulfate
  11. filtrationfilter
  12. concentrationconcentrate

Sources & evidence

ORD record
ord-2d5d9852f2cc4ba6b1a065c6c4cd6ec2
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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