Ethanol → 6'-Chloro-4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile

HRID 1243786

반응식

HRID 1243786 반응식
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:3]=1[C:4]#[N:5].CCO.CCN(C(C)C)C(C)C.Cl.Cl.[CH3:29][N:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[CH:39]([OH:48])[CH2:40][NH:41][CH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>CCOC(C)=O>[Cl:1][C:2]1[N:9]=[C:8]([N:45]2[CH2:46][CH2:47][CH:42]([NH:41][CH2:40][CH:39]([OH:48])[C:31]3[N:30]([CH3:29])[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=3)[CH2:43][CH2:44]2)[CH:7]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:3]=1[C:4]#[N:5]

참가 물질

6

반응물 4

HCID 702EthanolHCID 81531Diisopropylethylamine2회HCID 27367262,6-Dichloro-4-(trifluoromethyl)nicotinonitrileHCID 219280571-(1-methyl-1H-benzoimidazol-2-yl)-2-(piperidin-4-ylamino)-ethanol dihydrochloride

생성물 1

HCID 219281596'-Chloro-4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile수율 62.5%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

2,6-Dichloro-4-trifluoromethyl-nicotinonitrile (277 mg, 1.15 mmol) was dissolved into 10 mL of absolute EtOH and cooled in a wet ice bath. To this was added DIPEA (1.74 mL, 10 mmol) and 1-(1-methyl-1H-benzoimidazol-2-yl)-2-(piperidin-4-ylamino)-ethanol dihydrochloride (400 mg, 1.15 mmol). The mixture was stirred for 2 h. LC-MS anlysis indicated formation of the product. The reaction mixture was concentrated on a rotary evaporator and the residue was dissolved in CH2Cl2 and applied to a SiO2 column and purified (0–10% MeOH/CH2Cl2) to give an oil, still contaminated with DIPEA. Trituration with EtOAc gave 344 mg, 62.4% of 6′-chloro4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile.

후처리

  1. temperaturecooled in a wet ice bath
  2. concentrationThe reaction mixture was concentrated on a rotary evaporator
  3. dissolutionthe residue was dissolved in CH2Cl2
  4. custompurified (0–10% MeOH/CH2Cl2)
  5. customto give an oil

출처 및 근거

ORD 기록
ord-3a8a1fc1b9294e108a5b8bef96f1c4f9
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07119102B2

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