Diisopropylethylamine → (2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate

HRID 1008855노트

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HRID 1008855 반응식
Cl.[Cl:2][C:3]1[C:4]([O:15][C@H:16]2[CH2:20][NH:19][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17]2)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][CH:9]=[C:8]([O:13][CH3:14])[CH:7]=2.[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40](O)=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40]([N:19]1[CH2:20][C@H:16]([O:15][C:4]2[C:3]([Cl:2])=[N:12][C:11]3[C:6](=[CH:7][C:8]([O:13][CH3:14])=[CH:9][CH:10]=3)[N:5]=2)[CH2:17][C@H:18]1[C:21]([O:23][CH3:24])=[O:22])=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59287076L-Valine, 3-methyl-N-[[[(1R,2R)-2-(4-penten-1-yl)cyclopropyl]oxy]carbonyl]-HCID 78358295Methyl (2S)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate hydrochloride

생성물 1

HCID 78358296(2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate수율 96%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
20 °C

실험 절차

A solution (0.2 M) of methyl (4R)-4-[(3-chloro-7-methoxyquinoxalin-2-yl)oxy]-L-prolinate hydrochloride in DMF was treated with 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valine (1.1 eq), DIEA (5 eq) and HATU (1.2 eq). The resulting mixture was stirred at 20° C. for 5 h, then diluted with EtOAc. The organic layer was separated and washed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine. The dried organic phase was concentrated under reduced pressure to give a residue that was purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether) to furnish the title compound (96%) as an oil. MS (ES+) m/z 604 (M+H)+

후처리

  1. customThe organic layer was separated
  2. washwashed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine
  3. concentrationThe dried organic phase was concentrated under reduced pressure
  4. customto give a residue that
  5. customwas purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether)

출처 및 근거

ORD 기록
ord-95eae81013b14d80bc711c1bfcbc8d1b
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07973040B2

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