HCID 57504499, compound → (2S)-3-cyclobutyloxy-N-(5-methylpyrazin-2-yl)-2-[1-[3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxypropanamide

HRID 1098006Notes

Reaction equation

HRID 1098006 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:35]([F:38])([F:37])[F:36])[C:5]([N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([O:17][C@@H:18]([CH2:29][O:30][CH:31]4[CH2:34][CH2:33][CH2:32]4)[C:19]([NH:21][C:22]4[CH:27]=[N:26][C:25]([CH3:28])=[CH:24][N:23]=4)=[O:20])=[C:11]3[CH:10]=[N:9]2)=[N:6][CH:7]=1>[Pd].C(O)C>[CH:31]1([O:30][CH2:29][C@H:18]([O:17][C:16]2[C:11]3[CH:10]=[N:9][N:8]([C:5]4[C:4]([C:35]([F:37])([F:38])[F:36])=[CH:3][CH:2]=[CH:7][N:6]=4)[C:12]=3[N:13]=[CH:14][N:15]=2)[C:19]([NH:21][C:22]2[CH:27]=[N:26][C:25]([CH3:28])=[CH:24][N:23]=2)=[O:20])[CH2:32][CH2:33][CH2:34]1

Participants

4

Reactant 1

HCID 57504499HCID 57504499, compound

Product 1

HCID 57504498(2S)-3-cyclobutyloxy-N-(5-methylpyrazin-2-yl)-2-[1-[3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxypropanamideYield 32%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

10% Palladium on carbon (200 mg, 1.88 mmol) and (2S)-2-(1-(5-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-cyclobutoxy-N-(5-methylpyrazin-2-yl)propanamide (Example 138) (501 mg, 0.91 mmol) in ethanol was stirred under an atmosphere of hydrogen at ambient temperature for 20 hours. The mixture was filtered and fresh catalyst (200 mg) added and the mixture stirred under hydrogen atmosphere for 8 hours. The mixture was filtered, triethylamine (1 mL) added, and the mixture evaporated. The residue was purified by flash silica chromatography eluting with ethyl acetate to give the product (150 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 1.46-1.60 (1H, m), 1.64-1.71 (1H, m), 1.92-1.97 (2H, m), 2.18-2.23 (2H, m), 2.54 (3H, s), 3.98-4.07 (3H, m), 6.05 (1H, t), 7.65-7.68 (1H, m), 8.12 (1H, d), 8.29 (1H, dd), 8.44 (1H, s), 8.62-8.67 (1H, m), 8.65 (1H, s), 8.89 (1H, dd), 9.45 (1H, d); m/z (ESI+) (M+H)+=515; HPLC tR=2.25 min.

Workup

  1. filtrationThe mixture was filtered
  2. additionfresh catalyst (200 mg) added
  3. filtrationThe mixture was filtered
  4. additiontriethylamine (1 mL) added
  5. customthe mixture evaporated
  6. customThe residue was purified by flash silica chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-e9848d091ca449ef8e4433131a8b40bb
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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