5-Fluoroindole-2-carboxylic acid → 5-Fluoro-1H-indole-2-carboxylic acid [(1S)-(4-fluoro-benzyl)-2-morpholin-4-yl-2-oxo-ethyl]-amide

HRID 651116Notes

Reaction equation

HRID 651116 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:4]([N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)=[O:5].[F:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25]([C:30](O)=[O:31])=[CH:24]2>>[F:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][C@H:3]([NH:2][C:30]([C:25]2[NH:26][C:27]3[C:23]([CH:24]=2)=[CH:22][C:21]([F:20])=[CH:29][CH:28]=3)=[O:31])[C:4]([N:6]2[CH2:11][CH2:10][O:9][CH2:8][CH2:7]2)=[O:5])=[CH:14][CH:15]=1

Participants

3

Reactant 2

HCID 18205-Fluoroindole-2-carboxylic acidHCID 69687112(S)-2-Amino-3-(4-fluoro-phenyl)-1-morpholin-4-yl-propan-1-one hydrochloride

Product 1

HCID 573120765-Fluoro-1H-indole-2-carboxylic acid [(1S)-(4-fluoro-benzyl)-2-morpholin-4-yl-2-oxo-ethyl]-amide

Procedure

(S)-2-Amino-3-(4-fluoro-phenyl)-1-morpholin-4-yl-propan-1-one hydrochloride (0.48 mmol) and 5-fluoro-1H-indole-2-carboxylic acid (0.48 mmol) were coupled according to Procedure A (0-25° C. reaction temperature, 48 hour reaction time, washed with acid first then base) and the product purified by chromatography on silica gel eluted with 20, 30, 40, 50 and 75% ethyl acetate in hexanes. Yield 189 mg, 95%; HPLC (60/40) 4.76 minutes (97%); PBMS 414 (MH+, 100%);

Workup

  1. custom0-25° C. reaction temperature, 48 hour reaction time
  2. washwashed with acid first
  3. custombase) and the product purified by chromatography on silica gel
  4. washeluted with 20, 30, 40, 50 and 75% ethyl acetate in hexanes
  5. customHPLC (60/40) 4.76 minutes (97%)

Sources & evidence

ORD record
ord-a36086da31f3424f8a8380b305fdf23f
Source dataset
uspto-grants-2001_08
Patent number
US06277877B1

Reaction notes

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