Pyridine → (R)-methyl 2-(3-(4-(2-fluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate

HRID 75839

Reaction equation

HRID 75839 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH:15][C@H:16]([CH:21]([CH3:23])[CH3:22])[C:17]([O:19][CH3:20])=[O:18])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.N1C=CC=CC=1.[F:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37](Cl)(=[O:39])=[O:38]>C(Cl)Cl>[F:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH:15][C@H:16]([CH:21]([CH3:23])[CH3:22])[C:17]([O:19][CH3:20])=[O:18])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1)(=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 1049PyridineHCID 1377612-Fluorobenzenesulphonyl chlorideHCID 67352792(R)-methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate

Product 1

HCID 67355864(R)-methyl 2-(3-(4-(2-fluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoateYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 500 mg (1.57 mmol) of (R)-methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate (example 151, step 3) in DCM, 1.2 eq of pyridine was added and stirred for 10 minutes, then 368 mg (1.89 mmol) 2-fluorobenzene-1-sulfonyl chloride was added and the reaction mixture was stirred for 3 hours. DCM was removed under vacuum, the reaction mixture was washed with 1NHCl and extracted with EtOAc. The organic layer was concentrated and purified by precipitation using DCM and petroleum ether to yield 410 mg (86%) of title compound. MS (ESI): m/z 476(M+H)+; 1HNMR (DMSO-d6, 300 MHz): δ 11.039 (s, 1H), 9.215 (d, 1H), 7.942 (m, 1H), 7.805 (d, 2H), 7.718 (m, 1H), 7.625 (s, 1H), 7.465 (m, 2H), 7.271(d, 2H), 4.314 (t, 1H), 3.690 (s, 3H), 2.228 (m, 1H), 0.971 (d, 6H).

Workup

  1. stirringthe reaction mixture was stirred for 3 hours
  2. customDCM was removed under vacuum
  3. washthe reaction mixture was washed with 1NHCl and
  4. extractionextracted with EtOAc
  5. concentrationThe organic layer was concentrated
  6. custompurified by precipitation

Sources & evidence

ORD record
ord-55309ba916b148068439f137b36f3df1
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Linked notes

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