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4-Methylmorpholine → 1-{[1-(2-tert-Butoxycarbonylamino-non-8-enoyl)-4-(isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 346926
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HRID 346926 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH2:22]([O:24][C:25]([C:27]1([NH:32][C:33]([CH:35]2[CH2:39][CH:38]([O:40][C:41]3[C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[CH:44]=[CH:43][N:42]=3)[CH2:37][NH:36]2)=[O:34])[CH2:29][CH:28]1[CH:30]=[CH2:31])=[O:26])[CH3:23].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C.CCCCCC>[CH2:22]([O:24][C:25]([C:27]1([NH:32][C:33]([CH:35]2[CH2:39][CH:38]([O:40][C:41]3[C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[CH:44]=[CH:43][N:42]=3)[CH2:37][N:36]2[C:10](=[O:12])[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19])=[O:34])[CH2:29][CH:28]1[CH:30]=[CH2:31])=[O:26])[CH3:23]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11507316(2S)-N-Boc-amino-non-8-enoic acidHCID 1317262291-{[4-(Isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester, bis hydrochloride

생성물 1

HCID 68746749
1-{[1-(2-tert-Butoxycarbonylamino-non-8-enoyl)-4-(isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester
수율 79.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 21226206Ethyl acetate hexane용매

실험 절차

2(S)-tert-butoxycarbonylamino-8-nonenoic acid (purchased from RSP Amino Acids)(1.0 g, 3.68 mmol) dissolved in 100 mL of DMF was treated sequentially with 1-{[4-(isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester, bis hydrochloride (1.46 g, 3.68 mmol), N-methyl morpholine (1.4 mL, 12.9 mmol), and HATU (PE biosystems) (1.68 g, 4.42 mmol). The reaction mixture was stirred at rt under N2 for 24 h, and then concentrated in vacuo. The residue was partitioned between ethyl acetate and pH 4 buffer (biphthalate). The organic phase was washed with sat. aq. NaHCO3, dried (MgSO4), and concentrated in vacuo to give 2.2 g of the crude product. Flash chromatography (20–50% ethyl acetate/hexane) gave 1.9 g (79%) of 1-{[1-(2-tert-butoxycarbonylamino-non-8-enoyl)-4-(isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester as a glassy colorless solid:

후처리

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and pH 4 buffer (biphthalate)
  3. washThe organic phase was washed with sat. aq. NaHCO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give 2.2 g of the crude product

출처 및 근거

ORD 기록
ord-f1401eefb6f1455e90316b0f58e3400a
출처 데이터셋
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07173004B2

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