Toluene → (3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanal

HRID 880551Notes

Reaction equation

HRID 880551 reaction equation
[CH:1]1(/[CH:6]=[CH:7]/[CH:8]=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[N+](C1C=CC(C(O)=O)=CC=1)([O-])=O.C1(C)C=CC=CC=1.[NH:29]1[CH:33]=[C:32]([C:34]2[C:35]3[CH:42]=[CH:41][N:40]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:36]=3[N:37]=[CH:38][N:39]=2)[CH:31]=[N:30]1>>[CH:1]1([C@H:6]([N:29]2[CH:33]=[C:32]([C:34]3[C:35]4[CH:42]=[CH:41][N:40]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:36]=4[N:37]=[CH:38][N:39]=3)[CH:31]=[N:30]2)[CH2:7][CH:8]=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 4

HCID 1140TolueneHCID 61084-Nitrobenzoic AcidHCID 140680852-Propenal, 3-cyclopentyl-, (2E)-HCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidine

Product 1

HCID 42631347(3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanalYield 83.8%

Procedure

A solution of (2E)-3-cyclopentylacrylaldehyde (28, 327 mg, 2.50 mmol, 5.0 equiv), (2R)-2-bis[3,5-bis(trifluoromethyl)phenyl][(triethylsilyl)oxy]methylpyrrolidine ((R)-35, 32 mg, 0.050 mmol, 0.10 equiv) and 4-nitrobenzoic acid (8.5 mg, 0.050 mmol, 0.10 equiv) in anhydrous toluene (5.0 mL, 47 mmol) was stirred at room temperature for 10 min before 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (17, 158 mg, 0.50 mmol) was added. The resulting reaction mixture was stirred at room temperature for 24 h. When LCMS showed that the reaction was deemed complete, the reaction mixture was concentrated under reduced pressure. The residue was directly purified by Combiflash (SiO2) with 0-70% EtOAc/hexane gradient elution to give (3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanal ((R)-38, 184.1 mg, 219.8 mg theoretical, 83.8% yield) as a pale yellow viscous oil. For (R)-38: C23H33N5O2Si (MW, 439.63), LCMS (EI) m/e 440 (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 (SiO2) with 0-70% EtOAc/hexane gradient elution

Sources & evidence

ORD record
ord-eecfae390c5a4d76a610f200e501f863
Source dataset
uspto-grants-2015_03
Patent number
US08993582B2

Reaction notes

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