1,2-Dichloroethane → (S)-Methyl 2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

HRID 339234노트

반응식

HRID 339234 반응식
[NH2:1][C@@H:2]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:3]([N:5]1[C@H:14]([C:15](=[O:27])[NH:16][C@H:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][CH2:18]2)[CH2:13][C:12]2[C:7](=[CH:8][C:9]([C:28]([O:30][CH3:31])=[O:29])=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].[C:36]([O:40][C:41]([N:43]([CH3:49])[C@@H:44]([CH3:48])[C:45](O)=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[C:36]([O:40][C:41]([N:43]([CH3:49])[C@@H:44]([CH3:48])[C:45]([NH:1][C@@H:2]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:3]([N:5]1[C@H:14]([C:15](=[O:27])[NH:16][C@H:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][CH2:18]2)[CH2:13][C:12]2[C:7](=[CH:8][C:9]([C:28]([O:30][CH3:31])=[O:29])=[CH:10][CH:11]=2)[CH2:6]1)=[O:4])=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37]

참가 물질

9

반응물 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 86705868(S)-Methyl 2-((S)-2-amino-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

생성물 1

HCID 86705869(S)-Methyl 2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate수율 100%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

To a 0° C. solution of (S)-methyl 2-((S)-2-amino-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (966 mg, 2.02 mmol) and (S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid (Advanced ChemTech, 411 mg, 2.02 mmol) in DMF (20 mL) was added EDC (465 mg, 2.43 mmol), followed by HOAt (330 mg, 2.43 mmol). NMM (667 μl, 6.07 mmol) was then added, and the resulting reaction mixture was stirred at 0° C. for 30 min, then warmed to room temperature and stirred for 4 h. The reaction mixture was then poured into a separatory funnel containing EtOAc and sat. aq. NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with 1N HCl (2×) and 10% LiCl, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (1.34 g, 2.02 mmol, 100%) as a light yellow foam, which was used without further purification. MS (ESI+) m/z 663.3 (M+H)+.

후처리

  1. customthe resulting reaction mixture
  2. temperaturewarmed to room temperature
  3. stirringstirred for 4 h
  4. additionThe reaction mixture was then poured into a separatory funnel
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washThe combined organic extracts were washed with 1N HCl (2×) and 10% LiCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-adf445424fc646538ee76c3b6d8c837f
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889712B2

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