Diisopropylethylamine → 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide

HRID 1750173노트

반응식

HRID 1750173 반응식
[CH2:1]([CH:3]([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([OH:17])=O)=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:18][C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[CH2:4][CH3:5])[CH3:2].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[NH2:44][C@@H:45]([CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:46][C:47]#[N:48].S([O-])(O)(=O)=O.[Na+]>CN(C=O)C.O.C(Cl)CCl>[C:47]([CH2:46][C@@H:45]([NH:44][C:15]([C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]([CH2:18][C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[N:8][C:9]=2[CH:14]=1)=[O:17])[CH2:49][CH:50]([CH3:52])[CH3:51])#[N:48]

참가 물질

9

반응물 5

HCID 81531Diisopropylethylamine2회HCID 181649HOAtHCID 516919Sodium BisulfateHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acidHCID 86714386(S)-3-Amino-5-methyl-hexanenitrile-hydrochloride

생성물 1

HCID 867143851-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide수율 90%

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4.93 g of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid in 50 ml of dry DMF 2.04 g of HOAT, 3.45 g of EDC and 4.35 ml of DIPEA were added at 0° C. After 30 min 3.29 g of (S)-3-Amino-5-methyl-hexanenitrile-hydrochloride and 4.35 ml of DIPEA were added and the reaction was stirred at rt for 4 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 M aqueous sodium hydrogensulphate solution. The reaction was extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. 5.90 g (90%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide were obtained.

후처리

  1. extractionThe reaction was extracted with ethyl acetate three times
  2. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5b1693a13d9a454196d244c133826784
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156796B2

반응 노트

불러오는 중…