m-Tolyl isocyanate → HCID 22346681, compound

HRID 897532Notes

Reaction equation

HRID 897532 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([F:18])[CH:12]=3)[C:3]=12.[C:32]1([CH3:41])[CH:37]=[CH:36][CH:35]=[C:34]([N:38]=[C:39]=[O:40])[CH:33]=1>N1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:39]([NH:38][C:34]4[CH:33]=[C:32]([CH3:41])[CH:37]=[CH:36][CH:35]=4)=[O:40])=[C:13]([F:18])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 69303m-Tolyl isocyanateHCID 22347390HCID 22347390, compound

Product 1

HCID 22346681HCID 22346681, compoundYield 30.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-[4-amino-3-(4-amino-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (600 mg, 1.41 mmol) was dissolved in pyridine (25 mL) and cooled to 0° C. m-Tolylisocyanate (206 mg, 1.54 mmol) was added and the reaction was stirred at 0° C. for 2.5 hours. The reaction mixture was concentrated under reduced pressure to yield the crude product as a brownish-yellow foam (841 mg). Purification by column chromatography on silica gel using a 25% to 50% ethyl acetate/heptane gradient followed by 5% methanol/dichloromethane as the eluent afforded tert-butyl 4-(4-amino-3-{3-fluoro-4-[(3-toluidinocarbonyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate as a light yellow solid (243 mg, 0.434 mmol). HPLC-RT: 17.82 min. (flow rate: 1 mL/min λ=254 nm Gradient: 5% to 85% acetonitrile/0.1M aqueous ammonium acetate gradient over 20 min.; Deltapak C18, 300 A, 5 μm, 150×3.9 mm column); m/z (MH+)=561.4.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto yield the crude product as a brownish-yellow foam (841 mg)
  4. customPurification by column chromatography on silica gel using a 25% to 50% ethyl acetate/heptane gradient

Sources & evidence

ORD record
ord-13f8488163e94c8f8dbe9ecd881e0ed6
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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