Triethylamine → 2-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[(7as)-3-oxotetrahydro-1h-pyrrolo[1,2-c]imidazol-2(3h)-yl]-3-pyridinyl}-n,2-dimethylpropanamide

HRID 421276Notes

Reaction equation

HRID 421276 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C:13]([CH3:40])([CH3:39])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([NH:32][CH2:33][C@@H:34]3[CH2:38][CH2:37][CH2:36][NH:35]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.Cl[C:51](Cl)([O:53]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([C:13]([CH3:39])([CH3:40])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[CH2:33][C@@H:34]4[CH2:38][CH2:37][CH2:36][N:35]4[C:51]3=[O:53])=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 592157702-[3,5-bis(trifluoromethyl)phenyl]-N-(4-(4-fluoro-2-methylphenyl)-6-{[(2S)-2-pyrrolidinylmethyl]amino}-3-pyridinyl)-N,2-dimethylpropanamide

Product 1

HCID 160639992-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[(7as)-3-oxotetrahydro-1h-pyrrolo[1,2-c]imidazol-2(3h)-yl]-3-pyridinyl}-n,2-dimethylpropanamideYield 37.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

The starting 2-[3,5-bis(trifluoromethyl)phenyl]-N-(4-(4-fluoro-2-methylphenyl)-6-{[(2S)-2-pyrrolidinylmethyl]amino}-3-pyridinyl)-N,2-dimethylpropanamide (D62, 38 mg, 0.064 mmol) was dissolved in 1 mL of anhydrous dichloromethane and treated with triethylamine (20 μL, 0.143 mmol). The solution was brought to 0° C. and triphosgene (10 mg, 0.034 mmol) was added. The reaction was stirred at 0° C. for 15 min, then brought to room temperature. After 24 h, the reaction was diluted with dichloromethane (10 mL) and extracted with brine. The organics were collected and the solvent removed. The product was isolated by flash chromatography (silica, cyclohexane:EtOAc 80:20 to EtOAc). Thus were obtained 8 mg of the target compound.

Workup

  1. customwas brought to 0° C.
  2. custombrought to room temperature
  3. waitAfter 24 h
  4. extractionextracted with brine
  5. customThe organics were collected
  6. customthe solvent removed
  7. customThe product was isolated by flash chromatography (silica, cyclohexane:EtOAc 80:20 to EtOAc)

Sources & evidence

ORD record
ord-68554c41a5d445eaa5920f338281bc55
Source dataset
uspto-grants-2012_01
Patent number
US08097618B2

Reaction notes

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