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

HRID 1043421

Reaktionsgleichung

Reaktionsgleichung von HRID 1043421
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]([CH3:66])([CH3:65])[C@H:52]([NH:56][C:57]([O:59][CH2:60][CH2:61][CH2:62][CH:63]=[CH2:64])=[O:58])[C:53](O)=[O:54].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:50][C:51]([CH3:66])([CH3:65])[C@H:52]([NH:56][C:57]([O:59][CH2:60][CH2:61][CH2:62][CH:63]=[CH2:64])=[O:58])[C:53]([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:54]

Komponenten

6

Edukt 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 453799283-Methyl-N-{[(pent-4-en-1-yl)oxy]carbonyl}-L-valineHCID 59266525(2S,4R)-methyl 4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate

Produkt 1

HCID 59266568(2S,4R)-methyl 1-((S)-3,3-dimethyl-2-((pent-4-enyloxy)carbonylamino)butanoyl)-4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylateAusbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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)-3,3-dimethyl-2-((pent-4-enyloxy)carbonylamino)butanoic acid (180 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 the product (2S,4R)-methyl 1-((S)-3,3-dimethyl-2-((pent-4-enyloxy)carbonylamino)butanoyl)-4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate (251 mg, 0.446 mmol, 75% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.96-1.00 (m, 1H) 1.04-1.10 (m, 1H) 1.11-1.21 (m, 7H) 1.64-1.79 (m, 2H) 2.06-2.20 (m, 2H) 2.52 (dd, J=13.30, 8.78 Hz, 1H) 2.83-3.04 (m, 4H) 3.72-3.82 (m, 3H) 3.96-4.12 (m, 3H) 4.15-4.21 (m, 1H) 4.31-4.41 (m, 1H) 4.86-5.10 (m, 3H) 5.19-5.30 (m, 1H) 5.41 (d, J=9.79 Hz, 1H) 5.67-5.87 (m, 2H) 6.61-6.76 (m, 1H) 7.28-7.44 (m, 7H) 7.61-7.71 (m, 1H). LCMS: r.t.=2.18 min., [M+H]+=563 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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-deee361d807447899a9fa425b8ed824e
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563505B2

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