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 1467457ノート

反応式

HRID 1467457 の反応式
[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

参加物

5

反応物 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

生成物 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]propanal収率 83.8%

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a0e6444b17644ef495d6ef30f9e57d3d
出典データセット
uspto-grants-2015_04
特許番号
US09000161B2

反応ノート

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