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

HRID 334211Notes

Reaction equation

HRID 334211 reaction equation
[CH:1]1(/[CH:6]=[CH:7]/[CH:8]=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(Cl)Cl.[C:14]([O:20][CH2:21][N:22]1[C:26]2[N:27]=[CH:28][N:29]=[C:30]([C:31]3[CH:32]=[N:33][NH:34][CH:35]=3)[C:25]=2[CH:24]=[CH:23]1)(=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16]>[N+](C1C=CC(C(O)=O)=CC=1)([O-])=O>[C:14]([O:20][CH2:21][N:22]1[C:26]2[N:27]=[CH:28][N:29]=[C:30]([C:31]3[CH:32]=[N:33][N:34]([C@@H:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:7][CH:8]=[O:9])[CH:35]=3)[C:25]=2[CH:24]=[CH:23]1)(=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 140680852-Propenal, 3-cyclopentyl-, (2E)-HCID 57868869(4-(1H-Pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate

Product 1

HCID 59420185(1R)-(4-(1-(1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateYield 80%

Reagents, catalysts & solvents 1

HCID 61084-Nitrobenzoic AcidCatalyst

Procedure

A solution of (2E)-3-cyclopentylacrylaldehyde (28, 345 mg, 2.50 mmol, 5.0 equiv), (2R)-2-bis[3,5-bis(trifluoromethyl)phenyl][(triethylsilyl)oxy]methylpyrrolidine ((R)-35, 16 mg, 0.025 mmol, 0.05 equiv) and 4-nitrobenzoic acid (4.3 mg, 0.025 mmol, 0.05 equiv) in anhydrous chloroform (CHCl3, 2.0 mL, 25 mmol) was stirred at room temperature for 10 min before [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (5, 0.150 g, 0.50 mmol) was added. The resulting reaction mixture was stirred at room temperature for 23 h. After LCMS showed that the reaction was deemed complete, the reaction mixture was concentrated under reduced pressure. The residue was directly purified by Combiflash with 0-80% EtOAc/hexane gradient elution to afford (1R)-(4-(1-(1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate ((R)-37, 169 mg, 211.8 mg theoretical, 80% yield) as a pale yellow foam. For (R)-37: C23H29N5O3 (MW, 423.51), LCMS (EI) m/e 424 (M++H).

Workup

  1. additionwas added
  2. customThe resulting reaction mixture
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. customThe residue was directly purified by Combiflash with 0-80% EtOAc/hexane gradient elution

Sources & evidence

ORD record
ord-48521e64f24e4b7c9889de718319aef3
Source dataset
uspto-grants-2014_11
Patent number
US08883806B2

Reaction notes

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