Trifluoroacetic acid → HCID 178501913, compound

HRID 1488051Notes

Reaction equation

HRID 1488051 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:12][N:11]([C:13]([C:15]3[CH:16]=[CH:17][C:18]([CH3:40])=[C:19]([C:21]4[N:22]=[C:23]([CH:27]5[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36](C)(C)C)=[O:34])[CH2:29][CH2:28]5)[NH:24][C:25]=4[CH3:26])[CH:20]=3)=[O:14])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.CC1C=CC(C(N2CC(C3C=CC(C#N)=CC=3)C2)=O)=CC=1C1NC(C2CCNCC2)=NC=1C.C(N(C(C)C)CC)(C)C.ClC(OC)=O>C(Cl)Cl.CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][N:11]([C:13]([C:15]3[CH:16]=[CH:17][C:18]([CH3:40])=[C:19]([C:21]4[NH:22][C:23]([CH:27]5[CH2:32][CH2:31][N:30]([C:33]([O:35][CH3:36])=[O:34])[CH2:29][CH2:28]5)=[N:24][C:25]=4[CH3:26])[CH:20]=3)=[O:14])[CH2:12]2)=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 90021783t-Butyl 4-(4-(5-(3-(4-cyanophenyl)azetidine-1-carbonyl)-2-methylphenyl)-5-methyl-1H-imidazol-2-yl)piperidine-1-carboxylate2×HCID 178425785HCID 178425785, compound

Product 1

HCID 178501913HCID 178501913, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(4-(5-(3-(4-cyanophenyl)azetidine-1-carbonyl)-2-methylphenyl)-5-methyl-1H-imidazol-2-yl)piperidine-1-carboxylate (compound 182.3, 227 mg, 0.42 mmol) in CH2Cl2 (10 mL), was added trifluoroacetic acid (2 ml). The reaction was stirred for 1.5 hours and concentrated under reduced pressure. The reaction mixture was neutralized with 2 mL Na2CO3 (1M) to afford the crude intermediate after lyophilization. A mixture of 4-(1-(4-methyl-3-(4-methyl-2-(piperidin-4-yl)-1H-imidazol-5-yl)benzoyl)azetidin-3-yl)benzonitrile (185 mg, 0.42 mmol) and diisopropyl ethylamine (363 μL, 2.1 mmol) were dissolved in DMF (6 mL). Methyl chloroformate (36 μL, 0.46 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction was concentrated, diluted with saturated NaH2PO4 (20 mL) and extracted with EtOAc (3×20 ml). The organic phase was washed by brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by preparative TLC with 10% methanol in dichloromethane and lyophilized to give 141 mg (67%, over 2 steps) of the title compound as a white solid. m/z (ES+) 498 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto afford the crude intermediate after lyophilization
  3. stirringthe mixture was stirred at room temperature for 1 hour
  4. concentrationThe reaction was concentrated
  5. additiondiluted with saturated NaH2PO4 (20 mL)
  6. extractionextracted with EtOAc (3×20 ml)
  7. washThe organic phase was washed by brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative TLC with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-613e34392c694443a61ee5f22797fdb8
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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