HCID 69093386, compound → GNE-0877

HRID 2409105Notes

Reaction equation

HRID 2409105 reaction equation
[CH3:1][C:2]([N:7]1[CH:11]=[C:10]([NH:12][C:13]2[N:18]=[C:17]([NH:19][CH3:20])[C:16]([C:21]([F:24])([F:23])[F:22])=[CH:15][N:14]=2)[C:9]([CH3:25])=[N:8]1)([CH3:6])[C:3]([NH2:5])=O>O=P(Cl)(Cl)Cl>[CH3:6][C:2]([N:7]1[CH:11]=[C:10]([NH:12][C:13]2[N:18]=[C:17]([NH:19][CH3:20])[C:16]([C:21]([F:22])([F:24])[F:23])=[CH:15][N:14]=2)[C:9]([CH3:25])=[N:8]1)([CH3:1])[C:3]#[N:5]

Participants

3

Reactant 1

HCID 69093386HCID 69093386, compound

Product 1

HCID 69093374GNE-0877Yield 42.1%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A stirred solution of 2-methyl-2-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)propanamide (250 mg, 0.7 mmol) in POCl3 (5 mL) was stirred at 90° C. for 1 hour. POCl3 was removed by evaporation, the mixture was added into ice/H2O (10 ml) and the pH of the solution was adjusted to 8 with sat.Na2CO3, the aqueous phase was extracted with ethyl acetate (5 mL×3). The combined organic phase was washed with sat. sodium chloride (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to dry to give a residue which was purified by recrystallization to give 2-methyl-2-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)propanenitrile (100 mg, 42%) as a white solid. 1H-NMR (300 MHz, DMSO-d6) δ ppm 9.18 (s, 1H), 8.29 (s, 1H), 8.14 (s, 1H), 7.10 (s, 1H), 2.91 (d, 3H), 2.22 (s, 3H), 1.94 (s, 2H). LCMS (m/z) ES+340 (m+1). Purity, 99.3% (HPLC at 214 nm); Ki=0.0005.

Workup

  1. customPOCl3 was removed by evaporation
  2. additionthe mixture was added into ice/H2O (10 ml)
  3. extractionNa2CO3, the aqueous phase was extracted with ethyl acetate (5 mL×3)
  4. washThe combined organic phase was washed with sat. sodium chloride (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto dry
  9. customto give a residue which
  10. customwas purified by recrystallization

Sources & evidence

ORD record
ord-aeba98843c4b466c95ac7649c205b6b2
Source dataset
uspto-grants-2014_08
Patent number
US08815882B2

Reaction notes

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