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

HRID 1043428Notes

Reaction equation

HRID 1043428 reaction equation
[CH2:1]([O:7][C:8]([NH:10][C@@H:11]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:12]([OH:14])=O)=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].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.[Cl:52][C:53]1[CH:54]=[CH:55][C:56]([CH:76]=[CH2:77])=[C:57]([C:59]2[CH:64]=[CH:63][C:62]([C@@:65]3([O:74][CH3:75])[CH2:69][NH:68][C@H:67]([C:70]([O:72][CH3:73])=[O:71])[CH2:66]3)=[CH:61][CH:60]=2)[CH:58]=1>C(Cl)Cl>[Cl:52][C:53]1[CH:54]=[CH:55][C:56]([CH:76]=[CH2:77])=[C:57]([C:59]2[CH:64]=[CH:63][C:62]([C@@:65]3([O:74][CH3:75])[CH2:69][N:68]([C:12](=[O:14])[C@@H:11]([NH:10][C:8]([O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6])=[O:9])[C:15]([CH3:18])([CH3:17])[CH3:16])[C@H:67]([C:70]([O:72][CH3:73])=[O:71])[CH2:66]3)=[CH:61][CH:60]=2)[CH:58]=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 45378514N-{[(Hex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valineHCID 59266544(2S,4R)-methyl 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-2-carboxylate

Product 1

HCID 59266536(2S,4R)-methyl 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-1-((S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxypyrrolidine-2-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (186 mg, 0.723 mmol), DIEA (0.303 mL, 1.735 mmol) and HATU (242 mg, 0.636 mmol) were added to a solution of (2S,4R)-methyl 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-2-carboxylate (215 mg, 0.578 mmol) in DCM (7 mL). The reaction was stirred at r.t. overnight. The reaction was evaporated and purified on the Biotage (10-50% EtOAc:Hex) to give (2S,4R)-methyl 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-1-((S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxypyrrolidine-2-carboxylate (13 mg, 0.201 mmol, 35% yield) as a colorless oil. LCMS: rt=2.58 min. [M+H]+=612; 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 (10-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-b296658fb1f54d02a8188ec4bf6494c9
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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