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Water → Tert-butyl (s)-1-((2s,4r)-4-(biphenyl-4-yl)-4-(butylthio)-2-((1r,2s)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

HRID 2425783
ノート
印刷プレビュー

反応式

HRID 2425783 の反応式
C1(C2C=CC=CC=2)C=CC([C@@:7]2([S:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:14]([CH3:17])([CH3:16])[CH3:15])[C@H:9]([C:27](O)=[O:28])[CH2:8]2)=CC=1.[C:41]1([CH3:51])[CH:46]=[CH:45][C:44](S(O)(=O)=O)=[CH:43][CH:42]=1.[NH2:52][C@:53]1([C:58]([NH:60][S:61]([CH:64]2[CH2:66][CH2:65]2)(=[O:63])=[O:62])=[O:59])[CH2:55][C@H:54]1[CH:56]=[CH2:57].O.CN(C(ON1N=N[C:78]2[CH:79]=[CH:80][CH:81]=N[C:77]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:51]1([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:81]=[CH:80][C:79]([C@@:7]2([S:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19](=[O:20])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[C:14]([CH3:15])([CH3:16])[CH3:17])[C@H:9]([C:27](=[O:28])[NH:52][C@:53]3([C:58](=[O:59])[NH:60][S:61]([CH:64]4[CH2:66][CH2:65]4)(=[O:63])=[O:62])[CH2:55][C@H:54]3[CH:56]=[CH2:57])[CH2:8]2)=[CH:78][CH:77]=1
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 5

HCID 962WaterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57998016(2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acidHCID 72163227Cyclopropanecarboxamide, 1-amino-N-(cyclopropylsulfonyl)-2-ethenyl-, (1R,2S)-, 4-methylbenzenesulfonate (1:1)

生成物 1

HCID 44476536Tert-butyl (s)-1-((2s,4r)-4-(biphenyl-4-yl)-4-(butylthio)-2-((1r,2s)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate収率 78%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To an iced slurry of (2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acid (60 mg, 0.105 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, p-toluenesulfonate salt, H2O (53.1 mg, 0.127 mmol), and HATU (60.1 mg, 0.158 mmol) in DCM (2 mL) was added N,N-diisopropylethylamine (0.055 mL, 0.316 mmol). The formed colorless slurry was stirred at room temperature for 5 h (it became light yellow solution). Diluted with DCM, quenched with 5% citric acid. The separated organic layer was washed with sat. sodium citrate and brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with gradient 5%-40% acetone-hexane to yield the desired product tert-butyl (S)-1-((2S,4R)-4-(biphenyl-4-yl)-4-(butylthio)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (69 mg, 0.082 mmol, 78% yield) as a white solid. 1H NMR (500 MHz, MeOD) ppm 0.83 (t, J=7.32 Hz, 3H), 1.03-1.12 (m, 10H), 1.19-1.36 (m, 4H), 1.35-1.49 (m, 4H), 1.48 (s, 9H), 1.88 (s, J=7.93, 5.49 Hz, 3H), 2.14-2.24 (m, 1H), 2.23-2.30 (m, 1H), 2.35 (t, J=11.60 Hz, 1H), 2.39-2.53 (m, 1H), 2.76-2.87 (m, 1H), 2.89-3.00 (m, 1H), 3.93 (dd, J=10.68, 641 Hz, 1H), 3.99 (d, J=10.99 Hz, 1H), 4.51 (d, J=10.07 Hz, 1H), 5.06 (d, J=10.99 Hz, 1H), 5.10-5.19 (m, 1H), 5.29 (d, J=17.09 Hz, 1H), 5.69-5.83 (m, 1H), 7.37 (t, J=7.32 Hz, 1H), 7.46 (t, J=7.78 Hz, 2H), 7.55-7.63 (m, 4H) 7.64-7.77 (m, 2H). LC-MS (retention time: 3.48 min, method B), MS m/z 781 (M+H).

後処理

  1. customquenched with 5% citric acid
  2. washThe separated organic layer was washed with sat. sodium citrate and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by BIOTAGE® column
  7. washeluted with gradient 5%-40% acetone-hexane

出典と根拠

ORDレコード
ord-4c1a5ba4a5f74eadac378df9924ef1a8
出典データセット
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07964560B2

反応ノート

読み込み中…

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