Triethylamine → 2-(3,5-Bis-trifluoromethyl-phenyl)-n-methyl-n-[(3s,4r)-4-phenyl-1-((s)-tetrahydro-furan-2-carbonyl)-pyrrolidin-3-yl]-isobutyramide

HRID 1365930Notes

Reaction equation

HRID 1365930 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([OH:8])=O.CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:43][C:44]([F:74])([F:73])[C:45]1[CH:46]=[C:47]([C:55]([CH3:72])([CH3:71])[C:56]([N:58]([CH3:70])[C@H:59]2[C@H:63]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[CH2:62][NH:61][CH2:60]2)=[O:57])[CH:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:50]=1>C1COCC1>[F:53][C:51]([F:52])([F:54])[C:49]1[CH:48]=[C:47]([C:55]([CH3:71])([CH3:72])[C:56]([N:58]([CH3:70])[C@H:59]2[C@H:63]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[CH2:62][N:61]([C:6]([C@@H:2]3[CH2:3][CH2:4][CH2:5][O:1]3)=[O:8])[CH2:60]2)=[O:57])[CH:46]=[C:45]([C:44]([F:43])([F:73])[F:74])[CH:50]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 446666Tetrahydro-2-furoic acid, (-)-HCID 59840126Rac-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-n-((3s,4r)-4-phenyl-pyrrolidin-3-yl)-isobutyramide

Product 1

HCID 872119432-(3,5-Bis-trifluoromethyl-phenyl)-n-methyl-n-[(3s,4r)-4-phenyl-1-((s)-tetrahydro-furan-2-carbonyl)-pyrrolidin-3-yl]-isobutyramideYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-tetrahydro-furan-2-carboxylic acid (described in J. Med. Chem., 1995, 38(15, 2830) (5.0 mg, 0.043 mmol) in THF (2 ml) at RT were added Et3N (12 μl, 0.086 mmol), BOP (25 mg, 0.057 mmol) and rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-((3S,4R)-4-phenyl-pyrrolidin-3-yl)-isobutyramide (Intermediate VII-1) (20 mg, 0.043 mmol). Stirring was continued at 40° C. for 48 hours. Concentration and purification by preparative HPLC afforded 5.1 mg (25%) of the title compound.

Workup

  1. concentrationConcentration and purification by preparative HPLC

Sources & evidence

ORD record
ord-647ef6ae4c2e4db2aa9db48d9334eede
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

Loading…