1,2-Dichloroethane → tert-Butyl 4-(5-((5S)-3-(3,3-dimethylbutyl)-4-oxo-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)thiazolidin-2-yl)thiazol-2-yl)piperidine-1-carboxylate

HRID 1695924

반응식

HRID 1695924 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][C:16]([CH:19]3[N:23]([CH2:24][CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:22](=[O:30])[C@H:21]([CH2:31][C:32](O)=[O:33])[S:20]3)=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[NH:58]1[CH2:63][CH2:62][CH:61]([N:64]2[CH2:70][CH2:69][C:68]3[CH:71]=[CH:72][CH:73]=[CH:74][C:67]=3[NH:66][C:65]2=[O:75])[CH2:60][CH2:59]1>C(Cl)Cl>[CH3:29][C:26]([CH3:28])([CH3:27])[CH2:25][CH2:24][N:23]1[C:22](=[O:30])[C@H:21]([CH2:31][C:32](=[O:33])[N:58]2[CH2:59][CH2:60][CH:61]([N:64]3[CH2:70][CH2:69][C:68]4[CH:71]=[CH:72][CH:73]=[CH:74][C:67]=4[NH:66][C:65]3=[O:75])[CH2:62][CH2:63]2)[S:20][CH:19]1[C:16]1[S:15][C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[N:18][CH:17]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 577743682-((5S)-2-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazol-5-yl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid

생성물 1

HCID 25207442tert-Butyl 4-(5-((5S)-3-(3,3-dimethylbutyl)-4-oxo-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)thiazolidin-2-yl)thiazol-2-yl)piperidine-1-carboxylate수율 75.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 2-((5S)-2-(2-(1-(tert-Butoxycarbonyl)piperidin-4-yl)thiazol-5-yl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid (360 mg, 0.7 mmol, 1 eq) in DCM (8 mL) was added HOBt (162 mg, 1.06 mmol, 1.5 eq), EDC (202 mg, 1.06 mmol, 1.5 eq), DIEA (364 mg, 2.8 mmol, 4 eq) and 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (207 mg, 0.84 mmol, 1.2 eq). The resulting mixture was stirred at room temperature for 18 hr. The reaction mixture was diluted with DCM (10 mL) and washed with water (5 mL), brine (5 mL), dried (MgSO4) then concentrated in vacuo. The residue was purified by column chromatography over silica gel eluted with 0 to 10% MeOH in DCM to afford 390 mg of compound I-492 in 75% yield. (M+1) 739. 1H NMR (CDCl3) δ 7.19-6.91 (m, 5H), 6.75 (d, J=7.8 Hz, 1H), 5.68 (m, 1H), 4.75 (m, 1H), 4.47 (m, 1H), 4.18 (m, 1H), 3.93 (m, 1H), 3.46-2.67 (m, 11H), 2.08 (m, 6H), 1.71 (m, 6H), 1.47 (m, 9H), 0.85 (m, 9H) ppm.

후처리

  1. washwashed with water (5 mL), brine (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationthen concentrated in vacuo
  4. customThe residue was purified by column chromatography over silica gel
  5. washeluted with 0 to 10% MeOH in DCM

출처 및 근거

ORD 기록
ord-afcf4fb36709467185c2eb51c99e636b
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163737B2

연결된 노트

불러오는 중…