Diisopropylethylamine → (2S,4R)-methyl 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-1-((S)-2-((2,2-dimethylhex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxypyrrolidine-2-carboxylate

HRID 1043442Notes

Reaction equation

HRID 1043442 reaction equation
[CH3:1][C:2]([CH3:20])([CH2:16][CH2:17][CH:18]=[CH2:19])[CH2:3][O:4][C:5]([NH:7][C@@H:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:9]([OH:11])=O)=[O:6].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:54][N:55]([CH3:81])[C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[CH:66][C:65]([C@@:68]3([O:77][CH3:78])[CH2:72][NH:71][C@H:70]([C:73]([O:75][CH3:76])=[O:74])[CH2:69]3)=[CH:64][CH:63]=2)=[C:58]([CH:79]=[CH2:80])[CH:57]=1>C(Cl)Cl>[CH3:81][N:55]([CH3:54])[C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:63]=[CH:64][C:65]([C@@:68]3([O:77][CH3:78])[CH2:72][N:71]([C:9](=[O:11])[C@@H:8]([NH:7][C:5]([O:4][CH2:3][C:2]([CH3:1])([CH3:20])[CH2:16][CH2:17][CH:18]=[CH2:19])=[O:6])[C:12]([CH3:15])([CH3:14])[CH3:13])[C@H:70]([C:73]([O:75][CH3:76])=[O:74])[CH2:69]3)=[CH:66][CH:67]=2)=[C:58]([CH:79]=[CH2:80])[CH:57]=1

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 45379499(S)-2-((((2,2-Dimethylhex-5-en-1-yl)oxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 59266550(2S,4R)-methyl 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-2-carboxylate

Product 1

HCID 59266538(2S,4R)-methyl 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-1-((S)-2-((2,2-dimethylhex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxypyrrolidine-2-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-((2,2-dimethylhex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (62 mg, 0.217 mmol), DIEA (0.076 mL, 0.434 mmol) and HATU (61 mg, 0.159 mmol) were added to a solution of (2S,4R)-methyl 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-2-carboxylate (55 mg, 0.145 mmol) in DCM (3 mL). The reaction was stirred at r.t. for 2 hrs. The reaction was evaporated and purified on the Biotage (10-45% EtOAc:Hex) to give (2S,4R)-methyl 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-1-((S)-2-((2,2-dimethylhex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxypyrrolidine-2-carboxylate (61 mg, 0.094 mmol, 65% yield) as a yellow oil. LCMS: rt=2.00 min. [M-OMe]+=616 and [M+H]+=648; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220.

Workup

  1. customThe reaction was evaporated
  2. custompurified on the Biotage (10-45% EtOAc:Hex)

Sources & evidence

ORD record
ord-fb448e4c11e44b11bc7aecccafc75858
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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