Dimethylacetamide → 4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile

HRID 1468849ノート

反応式

HRID 1468849 の反応式
Br[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C[C:29]([N:31](C)C)=O>CCOCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn]>[CH2:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][CH:12]([C@H:10]3[CH2:11][C@H:9]3[CH2:8][O:7][CH2:6][C:5]3[CH:26]=[CH:27][C:2]([C:29]#[N:31])=[CH:3][CH:4]=3)[CH2:13][CH2:14]2)=[N:23][CH:22]=1)[CH3:25]

参加物

8

反応物 2

HCID 31374DimethylacetamideHCID 711352722-[4-((1R,2R)-2-{[(4-bromobenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]-5-ethyl pyrimidine

生成物 1

HCID 711288064-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile

試薬・触媒・溶媒 5

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 3283Diethyl Ether溶媒

反応条件

温度
100 °C

実験手順

The product of example 54 (step A) (500 mg, 1.17 mmol), Pd2(dba)3 (43 mg, 0.046 mmol), dppf (51.5 mg, 0.093 mmol), Zn(CN)2 (89 mg, 0.755 mmol) and zinc dust (18 mg, 0.278 mmol) in DMA (1 mL) was evacuated and back-filled with argon (×3). The mixture was stirred at 100° C. for 4 h. The reaction was cooled to room temperature, diluted with Et2O and filtered through a pad of silica. The filtrate was concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate) to yield the title compound as a colorless gum. MS (ESI) m/z 377 [M+H]+.

後処理

  1. additionback-filled with argon (×3)
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through a pad of silica
  4. concentrationThe filtrate was concentrated under vacuum
  5. customto leave a residue which
  6. customwas purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate)

出典と根拠

ORDレコード
ord-7766252cd4214ae488dd8d1d329c47ad
出典データセット
uspto-grants-2015_04
特許番号
US09006228B2

反応ノート

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