Methyl (2S)-2-[1-[5-chloro-3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxypropanoate → Methyl (2S)-3-ethoxy-2-[1-[3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxypropanoate

HRID 1098139Notes

Reaction equation

HRID 1098139 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:27]([F:30])([F:29])[F:28])[C:5]([N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([O:17][C@@H:18]([CH2:23][O:24][CH2:25][CH3:26])[C:19]([O:21][CH3:22])=[O:20])=[C:11]3[CH:10]=[N:9]2)=[N:6][CH:7]=1>[Pd].CO>[CH2:25]([O:24][CH2:23][C@H:18]([O:17][C:16]1[C:11]2[CH:10]=[N:9][N:8]([C:5]3[C:4]([C:27]([F:28])([F:29])[F:30])=[CH:3][CH:2]=[CH:7][N:6]=3)[C:12]=2[N:13]=[CH:14][N:15]=1)[C:19]([O:21][CH3:22])=[O:20])[CH3:26]

Participants

4

Reactant 1

HCID 57504622Methyl (2S)-2-[1-[5-chloro-3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxypropanoate

Product 1

HCID 57504620Methyl (2S)-3-ethoxy-2-[1-[3-(trifluoromethyl)pyridin-2-yl]pyrazolo[4,5-e]pyrimidin-4-yl]oxypropanoateYield 54.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(2S)-Methyl 2-(1-(5-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxypropanoate (Intermediate Q2) (800 mg, 1.79 mmol) and 10% palladium on carbon (200 mg) in MeOH (30 mL) was stirred under an atmosphere of hydrogen for 24 hours. The mixture was filtered, 10% palladium on carbon (200 mg) and ammonium formate (1.0 g) were added and the mixture was heated to reflux for 2 hours. The mixture was allowed to cool and was filtered and evaporated. The residue was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane to afford the product (400 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 1.25 (3H, t), 3.62-3.73 (2H, m), 3.79 (3H, s), 4.00-4.11 (2H, m), 5.84 (1H, dd), 7.63-7.66 (1H, m), 8.27-8.29 (1H, m), 8.38 (1H, s), 8.58 (1H, s), 8.88-8.89 (1H, m); m/z (ESI+) (M+H)+=412; HPLC tR=2.13 min.

Workup

  1. filtrationThe mixture was filtered
  2. addition10% palladium on carbon (200 mg) and ammonium formate (1.0 g) were added
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 2 hours
  5. temperatureto cool
  6. filtrationwas filtered
  7. customevaporated
  8. customThe residue was purified by flash silica chromatography
  9. washeluting with 50 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-86a0fc4a97d74e84aa53e28b1fc4a19a
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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