Trifluoroacetic acid → HCID 178473785, compound

HRID 1488050Notes

Reaction equation

HRID 1488050 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(C)(C)C)=O)[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].F[C:42](F)(F)C(O)=O.CC1C=CC(C(N2CC(C3C=CC(C#N)=CC=3)C2)=O)=CC=1C1NC(C2CCNCC2)=NC=1C.C(OC(=O)C)(=O)C.C(N(CC)CC)C>C(Cl)Cl>[C:33]([N:30]1[CH2:31][CH2:32][CH:27]([C:23]2[NH:22][C:21]([C:19]3[CH:20]=[C:15]([CH:16]=[CH:17][C:18]=3[CH3:40])[C:13]([N:11]3[CH2:10][CH:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=4)[CH2:12]3)=[O:14])=[C:25]([CH3:26])[N:24]=2)[CH2:28][CH2:29]1)(=[O:35])[CH3:42]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 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 178473785HCID 178473785, compound

Reagents, catalysts & solvents 1

HCID 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, 475 mg, 0.88 mmol) in 20 mL DCM, was added trifluoroacetic acid (4 mL). The reaction was stirred for 1.5 hours, concentrated under reduced pressure and neutralized with 10 mL Na2CO3 (1M) to obtain a crude product 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 (252 mg, 0.57 mmol), acetic anhydride (71 μL, 0.75 mmol) and triethylamine (120 μL, 0.86 mmol) was stirred at room temperature for 16 hours. The reaction was concentrated under reduced pressure, then diluted with saturated NaH2PO4 (20 mL) and extracted with EtOAc (3×20 mL). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by preparative TLC with 10% methanol in dichloromethane and lyophilized to give 235 mg (80%-2 steps) of the title compound as a white solid. m/z (ES+) 482 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure and neutralized with 10 mL Na2CO3 (1M)
  2. customto obtain a crude product after lyophilization
  3. stirringwas stirred at room temperature for 16 hours
  4. concentrationThe reaction was concentrated under reduced pressure
  5. additiondiluted with saturated NaH2PO4 (20 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialThe organic phase was dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative TLC with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-8e8be8e10c464878b0dad1b67a5dc8c9
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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