(Z)-(4-(1-(3-Amino-1-cyclopentyl-3-oxoprop-1-enyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate → (R)-(4-(1-(3-Amino-1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 880534Notes

Reaction equation

HRID 880534 reaction equation
[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21](/[C:23](/[CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:24]\[C:25]([NH2:27])=[O:26])[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[H][H]>CO>[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21]([C@@H:23]([CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)[CH2:24][C:25]([NH2:27])=[O:26])[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3]

Participants

4

Reactant 2

HCID 59420169(Z)-(4-(1-(3-Amino-1-cyclopentyl-3-oxoprop-1-enyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateHCID 178418361HCID 178418361, compound

Product 1

HCID 59420152(R)-(4-(1-(3-Amino-1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

A solution of (4-{1-[(1Z)-3-amino-1-cyclopentyl-3-oxoprop-1-en-1-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate, (10, 500 mg) in methanol (MeOH, 8.0 mL) in a pressure glass tube was treated with the catalyst Ru(COD)(SL-A153-1)(CF3CO2)2 (6.6 mg) under nitrogen before the reaction mixture was pressurized with hydrogen gas to 50 bar pressure. The reaction mixture was stirred at 30° C. under this hydrogen pressure for 21 h. When HPLC analysis showed that the substrate was completely consumed, the reaction mixture was cooled down to room temperature. The enantiomeric excess of the reaction mixture was determined to be 98% ee (99% of the second peak, (R)-11; 1% of the first peak, (S)-11) by chiral HPLC analysis. The reaction mixture was then filtered through a thin silica gel pad and the pad was washed with methanol (5 mL). The filtrate was then concentrated under reduced pressure to dryness. The resultant foamy solid (470 mg) was analyzed by chiral HPLC analysis and result showed a 98.0% of enantiomeric excess favoring the second peak (99.0% of the second peak, (R)-11; 1.0% of the first peak, (S)-11).

Workup

  1. customwas completely consumed
  2. temperaturethe reaction mixture was cooled down to room temperature
  3. filtrationThe reaction mixture was then filtered through a thin silica gel pad
  4. washthe pad was washed with methanol (5 mL)
  5. concentrationThe filtrate was then concentrated under reduced pressure to dryness
  6. customresult

Sources & evidence

ORD record
ord-27c57b4e6fe2403e9732527d4d617acc
Source dataset
uspto-grants-2015_03
Patent number
US08993582B2

Reaction notes

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