Ethanolamine → 2-(2-(4-(1-(2-hydroxyethylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

HRID 1162764노트

반응식

HRID 1162764 반응식
[NH2:1][CH2:2][CH2:3][OH:4].[C:5]([C:8]1[C:9]([C:29]([F:32])([F:31])[F:30])=[N:10][N:11]([CH2:13][C:14]([NH:16][C:17]2[S:21][C:20]3[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[C:18]=2[C:26]([NH2:28])=[O:27])=[O:15])[CH:12]=1)(=O)[CH3:6].C([BH3-])#N.[Na+]>CO.CC(O)=O>[OH:4][CH2:3][CH2:2][NH:1][CH:5]([C:8]1[C:9]([C:29]([F:31])([F:32])[F:30])=[N:10][N:11]([CH2:13][C:14]([NH:16][C:17]2[S:21][C:20]3[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[C:18]=2[C:26]([NH2:28])=[O:27])=[O:15])[CH:12]=1)[CH3:6]

참가 물질

6

반응물 3

HCID 700EthanolamineHCID 5003444Sodium cyanoborohydrideHCID 595205152-(2-(4-acetyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

생성물 1

HCID 595205182-(2-(4-(1-(2-hydroxyethylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide수율 15%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 887Methanol용매

반응 조건

온도
100 °C

실험 절차

To a solution of 2-aminoethanol (103 mg, 1.689 mmol) in MeOH (1.5 mL), AcOH was added until the pH reached 5. 2-(2-(4-acetyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (50 mg, 0.121 mmol) was added before the addition of (7.6 mg, 0.121 mmol) of sodium cyanoborohydride. The reaction was heated by microwave irradiation to 100° C. for 20 min. The reaction mixture was filtered before purification by preparative reverse phase HPLC. The product fractions were acidified to pH 4 before applying to a strong cation exchange cartridge (500 mg). The cartridge was washed with DCM/MeOH (1:1) before eluting the product with 2M NH3 in MeOH. The solvent was removed in vacuo to give the title compound (8.3 mg, 0.018 mmol, 15%).

후처리

  1. filtrationThe reaction mixture was filtered before purification by preparative reverse phase HPLC
  2. washThe cartridge was washed with DCM/MeOH (1:1)
  3. washbefore eluting the product with 2M NH3 in MeOH
  4. customThe solvent was removed in vacuo

출처 및 근거

ORD 기록
ord-52d05392f21b4d8183c4988106b4e342
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820707B2

반응 노트

불러오는 중…