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 1043422Notes

Reaction equation

HRID 1043422 reaction equation
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]

Participants

6

Reactant 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

Product 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-carboxylateYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-c84dd42ec1f64a2281a7c8c938874952
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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