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 1959892노트

반응식

HRID 1959892 반응식
[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

참가 물질

5

반응물 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

생성물 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]propanal수율 83.8%

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-8070d6ed430d44b1b5c7523868930217
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410265B2

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