2-Fluorophenyl isocyanate → (S)-methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoate

HRID 75837Notes

Reaction equation

HRID 75837 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([N:15]([C@@H:17]([CH:22]([CH3:24])[CH3:23])[C:18]([O:20][CH3:21])=[O:19])[CH3:16])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]=[C:33]=[O:34]>C1COCC1>[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH:32][C:33](=[O:34])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([N:15]([C@@H:17]([CH:22]([CH3:24])[CH3:23])[C:18]([O:20][CH3:21])=[O:19])[CH3:16])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 855882-Fluorophenyl isocyanateHCID 67353570(S)-Methyl 2-(3-(4-aminophenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoate

Product 1

HCID 67355460(S)-methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoateYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

((S)-Methyl 2-(3-(4-aminophenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoate (170 mg. 0.513 mmol) was dissolved in THF (10 ml) and to it 2-fluorophenylisocyanate (105 mg. 0.770 mmol) was added. Reaction mixture was stirred at RT for 24 hours. THF was removed under reduced pressure to get pale brown residue, which was purified by column chromatography using EtOAc and CHCl3 as the solvent system to yield 160 mg (67%) of the title compound. MS: ES (−): m/z 467 (M−1); ES (+): m/z 469(M+1); 1HNMR (DMSO-d6, 300 MHz) δ: 9.356 (s, 1H), 8.648 (d, 1H), 8.176 (t, 1H), 7.906 (d, 2H), 7.631-7.448 (s, 1H+d, 2H), 7.287 (m, 1H), 7.185 (t, 1H), 7.065 (m, 1H), 4.738-4.164 (d, 1H), 3.734-3.702 (s, 3H), 3.151-2.963 (s, 3H), 2.339 (m, 1H), 1.030-0.877 (d, 3H(×2)).

Workup

  1. additionwas added
  2. customReaction mixture
  3. customTHF was removed under reduced pressure
  4. customto get pale brown residue, which
  5. customwas purified by column chromatography

Sources & evidence

ORD record
ord-81bcb25fb77147ff90b7eaf3fbc10055
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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