2-Fluoro-5-methylphenyl isocyanate → N-[4-(3-amino-1H-pyrazolo[3,4-c]pyridin-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea

HRID 1159450Notes

Reaction equation

HRID 1159450 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][CH:11]=[C:10]3[NH:14][N:15]=[C:16]([NH2:17])[C:9]=23)=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[N:26]=[C:27]=[O:28]>CN(C=O)C>[NH2:17][C:16]1[C:9]2[C:10](=[CH:11][N:12]=[CH:13][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:27]([NH:26][C:20]3[CH:21]=[C:22]([CH3:25])[CH:23]=[CH:24][C:19]=3[F:18])=[O:28])=[CH:7][CH:6]=2)[NH:14][N:15]=1

Participants

4

Reactant 2

HCID 27333772-Fluoro-5-methylphenyl isocyanateHCID 671274914-(4-Amino-phenyl)-1H-pyrazolo[3,4-c]pyridin-3-ylamine

Product 1

HCID 11494558N-[4-(3-amino-1H-pyrazolo[3,4-c]pyridin-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product from Example 1D (50 mg, 0.22 mmol) in DMF (1 mL) was treated with 1-fluoro-2-isocyanato-4-methyl-benzene (0.03 mL, 0.22 mmol) and stirred for 16 hours. The crude product was directly purified via preparative HPLC on an Agilent Zorbax Stablebond C-18 (7 micron particle size) preparative column using a solvent gradient of 30% to 100% acetonitrile in 0.1% aqueous TFA at a flow rate of 15 mL/minute. The product was further purified via silica gel chromatography eluting with 5% methanol/CH2Cl2 to provide 4 mg ofthe title compound. MS (ESI(+)) m/e 377 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.28 (s, 3H) 4.61 (s, 2H) 6.77-6.85 (m, 1H) 7.12 (dd, J=11.53, 8.14 Hz, 1H) 7.49 (d, J=8.81 Hz, 2H) 7.63 (d, J=8.48 Hz 2 H) 7.94 (s, 1H) 8.01 (dd, J=8.31, 1.86 Hz, 1H) 8.55 (d, J=2.71 Hz, 1H) 8.73 (s, 1H) 9.24 (s, 1H) 12.26 (s, 1H).

Workup

  1. customThe crude product was directly purified via preparative HPLC on an Agilent Zorbax Stablebond C-18 (7 micron particle size) preparative column
  2. customThe product was further purified via silica gel chromatography
  3. washeluting with 5% methanol/CH2Cl2

Sources & evidence

ORD record
ord-48e0335c24124f059d25db84f1ca85c5
Source dataset
uspto-grants-2010_10
Patent number
US07812166B2

Reaction notes

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