Dimethylformamide → 4-Methyl-2-((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidine-1-carbonyl)benzonitrile

HRID 60927

반응식

HRID 60927 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH3:17])[C@H:12]1[CH2:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1)=[O:10].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH3:59][N:60](C=O)C>[C-]#N.[C-]#N.[Zn+2].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]>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([C:59]#[N:60])=[C:3]([C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([CH3:17])[C@H:12]2[CH2:18][NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:22][N:21]=2)=[O:10])[CH:4]=1

참가 물질

6

반응물 3

HCID 6228DimethylformamideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 89739735(2-Bromo-5-methylphenyl)((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)methanone

생성물 1

HCID 1177277964-Methyl-2-((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidine-1-carbonyl)benzonitrile

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
150 °C

실험 절차

A mixture of (2-bromo-5-methylphenyl)((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)methanone (synthesized from Example A3, 0.35 g, 0.744 mmol), Zn(CN)2 (0.105 g, 0.818 mmol), Pd2(dba)3 (0.068 g, 0.074 mmol) and 2-dicyclohexylphophino-2′,6′-dimethoxybiphenyl (S-Phos; 0.076 g, 0.186 mmol) in wet DMF (DMF:H2O 10:1, 20 mL) was degassed and sealed and heated in a microwave reactor for 1 h at 150° C. The reaction was cooled to rt and the solvent was removed in vacuo. The crude was dissolved with EtOAc, washed with satd. aq. NaHCO3 and brine and dried over Na2SO4. The solvent was removed and the crude was purified in silica gel with 0˜100% EtOAc/Hex to obtain the title compound. ESI-MS (m/z): 417 [M+1]+.

후처리

  1. customwas degassed
  2. customsealed
  3. temperatureThe reaction was cooled to rt
  4. customthe solvent was removed in vacuo
  5. dissolutionThe crude was dissolved with EtOAc
  6. washwashed with satd
  7. dry with materialaq. NaHCO3 and brine and dried over Na2SO4
  8. customThe solvent was removed
  9. customthe crude was purified in silica gel with 0˜100% EtOAc/Hex

출처 및 근거

ORD 기록
ord-d492422dd2c14dcf9635045cacd804df
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440982B2

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