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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
ノート
印刷プレビュー

反応式

HRID 346926 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 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
収率 79.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21226206Ethyl acetate hexane溶媒

実験手順

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:

後処理

  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

出典と根拠

ORDレコード
ord-f1401eefb6f1455e90316b0f58e3400a
出典データセット
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07173004B2

反応ノート

読み込み中…

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