m-Tolyl isocyanate → HCID 22346737, compound

HRID 897542Notes

Reaction equation

HRID 897542 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([N:7]=[C:8]=[O:9])[CH:2]=1.[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:29]3[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]3)[N:19]=[C:20]([C:21]3[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=3)[C:13]=12>N1C=CC=CC=1>[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:29]3[CH2:30][CH2:31][C:32](=[O:35])[CH2:33][CH2:34]3)[N:19]=[C:20]([C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:8]([NH:7][C:3]4[CH:4]=[CH:5][CH:6]=[C:1]([CH3:10])[CH:2]=4)=[O:9])=[C:23]([F:28])[CH:22]=3)[C:13]=12

Participants

4

Reactant 2

HCID 69303m-Tolyl isocyanateHCID 22347187HCID 22347187, compound

Product 1

HCID 22346737HCID 22346737, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

m-Tolyl isocyanate (1.2 equiv., 37.7 mg, 0.283 mmol) was added to a solution of 4-[4-amino-3-(4-amino-3-fluorophenyl) 1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclohexanone (80.3 mg, 0.236 mmol) in pyridine. After 16 h at 40° C., the reaction was quenched with water (2 mL) and evaporated to dryness. Purification by preparative RP-HPLC (10% to 40% CH3CN in 0.1 N aqueous ammonium acetate, buffered to pH 4.5, over 60 min at 10 mL/min using a Waters Deltapak C18, 15 μm, 100×40 mm column, λ=254 mm) gave N-{4-[4-amino-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-fluorophenyl}-N′-(3-methylphenyl)urea (91 mg, 84%); 1H NMR (DMSO-d6, 400 MHz) δ 2.26 (2H, br t), 2.30 (3H, s), 2.43 (4H, m), 2.69 (2H, m), 5.26 (1H, m), 6.82 (1H, d), 7.18 (1H, t), 7.25 (1H, br d), 7.32 (1H, br s), 7.45 (2H, m), 8.26 (1H, s), 8.36 (1H, t), 8.72 (1H, d) and 9.05 (1H, s) and RP-HPLC (10 to 90% CH3CN in 0.1 N aqueous ammonium acetate, buffered to pH 4.5, over 12 min at 2 mL/min using a Waters Symmetry C18, 5 μm, 250×4.6 mm column) Rt=15.433 min, 97.9%

Workup

  1. customthe reaction was quenched with water (2 mL)
  2. customevaporated to dryness
  3. customPurification by preparative RP-HPLC (10% to 40% CH3CN in 0.1 N aqueous ammonium acetate
  4. waitbuffered to pH 4.5, over 60 min at 10 mL/min

Sources & evidence

ORD record
ord-6af3dbcaa7fa4fd9b2ed2866fcb6d57b
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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