Phenyl isocyanate → HCID 57485446, compound

HRID 1020372Notes

Reaction equation

HRID 1020372 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]([C:13]3[O:17][C:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH:20]([CH3:24])[CH2:19]4)=[N:15][C:14]=3[C:25]([F:28])([F:27])[F:26])=[O:12])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[C:29]1([N:35]=[C:36]=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl>[CH3:24][CH:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16]2[O:17][C:13]([C:11]([NH:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[N:1]([C:36]([NH:35][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:37])[N:2]=[CH:3]4)=[O:12])=[C:14]([C:25]([F:28])([F:27])[F:26])[N:15]=2)[CH2:19]1

Participants

4

Reactant 2

HCID 7672Phenyl isocyanate2×HCID 67390510HCID 67390510, compound

Product 1

HCID 57485446HCID 57485446, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 49 (0.060 g, 0.152 mmol) in anhydrous methylene chloride (1.52 mL) at room temperature under argon was added phenyl isocyanate (0.018 mL, 0.160 mmol). The reaction mixture was stirred at room temperature for 17 h and another portion of phenyl isocyanate (0.018 mL, 0.160 mmol) was added. After additional stirring at room temperature for 17 h, the reaction mixture was quenched with methanol (1.0 mL) and concentrated. Purification by silica gel chromatography (eluant: 100% methylene chloride to 100% EtOAc gradient) gave 32.7 mg (42% yield) of 5-[[2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolyl]carbonylamino]-N-phenyl-1H-indazole-1-carboxamide (50) as a white solid. 1H NMR (500 MHz, CD3OD) δ 8.31 (br d, 1H, J=8.8 Hz), 8.24 (m, 2H), 7.70 (m, 3H), 7.39 (br t, 2H, J=7.9 Hz), 7.16 (t, 1H, J=7.4 Hz), 4.90 (br s, 2H), 4.20 (m, 2H), 3.08 (td, 1H, J=12.4, 3.1 Hz), 2.75 (dd, 1H, J=12.3, 12.6 Hz), 1.89 (m, 1H), 1.82 (m, 1H), 1.74 (m, 1H), 1.65 (m, 1H), 1.23 (m, 1H), 1.01 (d, 3H, J=6.6 Hz). MS (M+1): 513.

Workup

  1. stirringAfter additional stirring at room temperature for 17 h
  2. customthe reaction mixture was quenched with methanol (1.0 mL)
  3. concentrationconcentrated
  4. customPurification by silica gel chromatography (eluant: 100% methylene chloride to 100% EtOAc gradient)

Sources & evidence

ORD record
ord-57bd62e31b574ca9be59107edff013b2
Source dataset
uspto-grants-2014_05
Patent number
US08716312B2

Reaction notes

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