Triethylamine → (1S)-1-{[4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2-methylpropylamine

HRID 1394921Notes

Reaction equation

HRID 1394921 reaction equation
C(OC([NH:8][C@H:9]([C:13](O)=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[F:56][C:57]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][C:58]=1[C:64]1[CH2:68][NH:67][CH:66]([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH:65]=1>CN(C=O)C>[F:56][C:57]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][C:58]=1[C:64]1[CH2:68][N:67]([C:13]([C@@H:9]([NH2:8])[CH:10]([CH3:12])[CH3:11])=[O:14])[CH:66]([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH:65]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 83693Boc-L-ValineHCID 2724699PyBOPHCID 590017764-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole

Product 1

HCID 58641407(1S)-1-{[4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2-methylpropylamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(tert-butoxycarbonyl)-L-valine (101 mg, 0.464 mmol, 2.00 equiv), PYBOP (243 mg, 0.467 mmol, 2.00 equiv), and triethylamine (0.163 mL, 1.17 mmol, 5.00 equiv) were added to a solution of 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole (24, 0.233 mmol, 1 equiv) in DMF (10 mL) at 23° C., and the resulting mixture was stirred for 20 hours. The reaction mixture was partitioned between a 3:1 mixture of saturated aqueous sodium bicarbonate solution and brine (50 mL) and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was dissolved in a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 mL), and the resulting solution was allowed to stand for 45 minutes, then concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TPA present) to provide (1S)-1-{[4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2-methylpropylamine (15-1) as a 1:1 mixture of diastereomers (tan gum) (isolated as the TFA salt). LRMS m/z (M+H) 357.2 found, 357.2 required.

Workup

  1. customThe reaction mixture was partitioned between a 3:1 mixture of saturated aqueous sodium bicarbonate solution and brine (50 mL) and ethyl acetate (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 mL)
  5. waitto stand for 45 minutes
  6. concentrationconcentrated
  7. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TPA present)

Sources & evidence

ORD record
ord-e24fe38245ef4d6eaffe685639b7eac3
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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