Diisopropylethylamine → (2S,4R)-methyl 1-((S)-2-((2,2-dimethylpent-4-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate

HRID 1043422ノート

反応式

HRID 1043422 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][O:26][C@:27]1([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[CH:48]=[CH2:49])=[CH:38][CH:37]=2)[CH2:31][NH:30][C@H:29]([C:32]([O:34][CH3:35])=[O:33])[CH2:28]1.[CH3:50][C:51]([CH3:68])([CH2:65][CH:66]=[CH2:67])[CH2:52][O:53][C:54]([NH:56][C@@H:57]([C:61]([CH3:64])([CH3:63])[CH3:62])[C:58](O)=[O:59])=[O:55].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:50][C:51]([CH3:68])([CH2:65][CH:66]=[CH2:67])[CH2:52][O:53][C:54]([NH:56][C@@H:57]([C:61]([CH3:63])([CH3:62])[CH3:64])[C:58]([N:30]1[CH2:31][C@:27]([O:26][CH3:25])([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[CH:48]=[CH2:49])=[CH:38][CH:37]=2)[CH2:28][C@H:29]1[C:32]([O:34][CH3:35])=[O:33])=[O:59])=[O:55]

参加物

6

反応物 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 57389288n-{[(2,2-Dimethylpent-4-en-1-yl)oxy]carbonyl}-3-methyl-l-valineHCID 59266525(2S,4R)-methyl 4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate

生成物 1

HCID 59266551(2S,4R)-methyl 1-((S)-2-((2,2-dimethylpent-4-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate収率 67.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

HATU (248 mg, 0.652 mmol) was added to a solution of, (2S,4R)-methyl 4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate (200 mg, 0.593 mmol), (S)-2-((2,2-dimethylpent-4-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (201 mg, 0.741 mmol) and DIEA (0.311 mL, 1.778 mmol) in DCM (8 mL) and stirred at r.t. 60 hours. The reaction was evaporated and purified on the Biotage (10-40% EtOAc:Hex) to give (2S,4R)-methyl 1-((S)-2-((2,2-dimethylpent-4-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate (235 mg, 0.398 mmol, 67% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.83-0.94 (m, 6H) 0.97-1.02 (m, 1H) 1.06-1.10 (m, 1H) 1.12-1.19 (m, 7H) 1.95-2.07 (m, 2H) 2.46-2.59 (m, 1H) 2.88 (d, J=12.80 Hz, 1H) 2.92-3.03 (m, 3H) 3.65-3.74 (m, 1H) 3.74-3.79 (m, 3H) 3.79-3.86 (m, 1H) 4.00-4.09 (m, 1H) 4.14-4.21 (m, 1H) 4.31-4.42 (m, 1H) 4.85-4.92 (m, 1H) 4.95-5.09 (m, 2H) 5.17-5.26 (m, 1H) 5.38-5.49 (m, 1H) 5.67-5.84 (m, 2H) 6.60-6.75 (m, 1H) 7.25-7.30 (m, 1H) 7.30-7.42 (m, 6H) 7.61-7.68 (m, 1H). LCMS: r.t.=2.25 min., [M+H]+=591 Phenomenex Luna S10 (3×50 mm); Solvent A=95% water 5% methanol—10 mM ammonium acetate, Solvent B=5% water—95% methanol—10 mM ammonium acetate; gradient=0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 ml/min; inj. vol.=10 ul; wavelength=220 nm.

後処理

  1. custom60 hours
  2. customThe reaction was evaporated
  3. custompurified on the Biotage (10-40% EtOAc:Hex)

出典と根拠

ORDレコード
ord-c84dd42ec1f64a2281a7c8c938874952
出典データセット
uspto-grants-2013_10
特許番号
US08563505B2

反応ノート

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