2,4-Difluorophenyl isocyanate → (S)-methyl 2-(2-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazole-4-carboxamido)-3-methylbutanoate

HRID 75856Notes

Reaction equation

HRID 75856 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[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])[N:12]=2)=[CH:4][CH:3]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[N:32]=[C:33]=[O:34]>C1COCC1>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[NH:32][C:33](=[O:34])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[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])[N:12]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 5932582,4-Difluorophenyl isocyanateHCID 67352540(S)-methyl 2-(2-(4-aminophenyl)thiazole-4-carboxamido)-3-methylbutanoate

Product 1

HCID 67352417(S)-methyl 2-(2-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazole-4-carboxamido)-3-methylbutanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-methyl 2-(2-(4-aminophenyl)thiazole-4-carboxamido)-3-methylbutanoate (150 mg, 0.450 mmol) was taken in 3 mL THF, to this 2,4-difluoro-1-isocyanatobenzene (76.8 mg, 0.495 mol) was added and stirred at RT for 3-4 hr. After completion of reaction solvent was removed under reduced pressure and the residue purified by column chromatography. Yield: 200 mg (91%). MS (ESI) m/z: 487(M−H)−; 1HNMR (DMSO-d6, 300 MHz): δ 9.369 (s, 1H), 8.594 (d, 1H), 8.316 (s, 1H), 8.291 (s, 1H), 8.126 (m, 1H), 8.023 (d, 2H), 7.640 (d, 2H), 7.372 (m, 1H), 7.106 (m, 1H), 4.431 (dd, 1H), 3.696 (s, 3H), 2.300 (m, 1H), 0.981 (dd, 6H).

Workup

  1. additionwas added
  2. customAfter completion of reaction solvent
  3. customwas removed under reduced pressure
  4. customthe residue purified by column chromatography

Sources & evidence

ORD record
ord-0def355d1c7e43f39507811fec355f7e
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

Loading…