Triethylamine → 1-[4-(3-Amino-1H-pyrazolo[3,4-b]pyridin-6-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea

HRID 556438Notes

Reaction equation

HRID 556438 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[NH:14][N:15]=[C:16]([NH2:17])[C:11]3=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=1[N:36]=[C:37]=[O:38]>C1COCC1>[NH2:17][C:16]1[C:11]2[C:12](=[N:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:37]([NH:36][C:27]4[CH:28]=[C:29]([C:32]([F:33])([F:35])[F:34])[CH:30]=[CH:31][C:26]=4[F:25])=[O:38])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[NH:14][N:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 178507390HCID 178507390, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

100 mg (0.44 mmol) of 6-(4-aminophenyl)-1H-pyrazolo[3,4-b]pyridin-3-ylamine are partially solubilized in 2.5 ml of anhydrous THF. The mixture is then degassed for 15 minutes with argon. 61.55 μl (44.93 mg, 0.44 mmol, 1 eq.) of triethylamine are subsequently added. The solution is once again degassed for 15 minutes. Finally, 64.22 μl (91 mg, 0.44 mmol, 1 eq.) of 2-fluoro-5-(trifluoromethyl)phenyl isocyanate are added dropwise. The mixture is stirred for 2 hours at ambient temperature under an inert atmosphere. After reaction, the mixture is filtered. The filtrate is concentrated. A beige solid is isolated. This crude product is subsequently purified on a C18 reverse-phase silica (13 g) column with an eluent gradient of 5% to 95% of acetonitrile in water. The fractions containing the expected product are lyophilized. A white solid is isolated (10 mg).

Workup

  1. customThe mixture is then degassed for 15 minutes with argon
  2. customThe solution is once again degassed for 15 minutes
  3. customAfter reaction
  4. filtrationthe mixture is filtered
  5. concentrationThe filtrate is concentrated
  6. customA beige solid is isolated
  7. customThis crude product is subsequently purified on a C18 reverse-phase silica (13 g) column with an eluent gradient of 5% to 95% of acetonitrile in water
  8. additionThe fractions containing the expected product
  9. customA white solid is isolated (10 mg)

Sources & evidence

ORD record
ord-d127445927234e37b4723b709a20434e
Source dataset
uspto-grants-2011_11
Patent number
US08058290B2

Reaction notes

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