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 1043422노트

반응식

HRID 1043422 반응식
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]

참가 물질

6

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 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

생성물 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-carboxylate수율 67.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-c84dd42ec1f64a2281a7c8c938874952
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563505B2

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