Water → Thiophene-3-carboxylic acid (6-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrazolo[3,4-b]pyridin-3-yl)amide

HRID 556443Notes

Reaction equation

HRID 556443 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=4[F:31])=[O:19])=[CH:13][CH:12]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[S:32]1[CH:36]=[CH:35][C:34]([C:37](Cl)=[O:38])=[CH:33]1.O>N1C=CC=CC=1>[F:31][C:22]1[CH:23]=[CH:24][C:25]([C:27]([F:28])([F:30])[F:29])=[CH:26][C:21]=1[NH:20][C:18](=[O:19])[NH:17][C:14]1[CH:15]=[CH:16][C:11]([C:7]2[N:6]=[C:5]3[NH:4][N:3]=[C:2]([NH:1][C:37]([C:34]4[CH:35]=[CH:36][S:32][CH:33]=4)=[O:38])[C:10]3=[CH:9][CH:8]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 962WaterHCID 27763773-Thenoyl chloride2×HCID 1785092201-[4-(3-Amino-1H-pyrazolo[3,4-b]pyridin-6-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea

Product 1

HCID 16095404Thiophene-3-carboxylic acid (6-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrazolo[3,4-b]pyridin-3-yl)amide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 1-[4-(3-amino-1H-pyrazolo[3,4-b]pyridin-6-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea (80.0 mg, 0.186 mmol) in pyridine (2 ml) is cooled to 5° C. under argon and thiophene-3-carboxylic acid chloride (27 mg, 0.186 mmol, 1.0 eq.) is added. The mixture is stirred at ambient temperature for 5.5 h. Another equivalent of thiophene-3-carboxylic acid chloride (27 mg, 0.186 mmol) is added and the mixture is stirred at ambient temperature overnight. The reaction is taken up with water, and then extracted with ethyl acetate. The organic phase is washed twice with a salt solution, dried with magnesium sulphate, and concentrated. An orange yellow solid is then obtained. The crude is purified on a silica column, with an eluent gradient of 0% to 5% of methanol in dichloromethane. A beige solid is obtained:

Workup

  1. stirringthe mixture is stirred at ambient temperature overnight
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed twice with a salt solution
  4. dry with materialdried with magnesium sulphate
  5. concentrationconcentrated
  6. customAn orange yellow solid is then obtained
  7. customThe crude is purified on a silica column, with an eluent gradient of 0% to 5% of methanol in dichloromethane
  8. customA beige solid is obtained

Sources & evidence

ORD record
ord-1d6b16d06edb4c19bb7f082454a9d9d6
Source dataset
uspto-grants-2011_11
Patent number
US08058290B2

Reaction notes

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