Formic Acid → HCID 178425786, compound

HRID 1488049Notes

Reaction equation

HRID 1488049 reaction equation
[CH3:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([N:8]2[CH2:11][CH:10]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[CH2:9]2)=[O:7])=[CH:4][C:3]=1[C:22]1[NH:26][C:25]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[N:24][C:23]=1[CH3:33].[CH:34](O)=O.C=O.O>C([O-])(O)=O.[Na+]>[CH3:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([N:8]2[CH2:11][CH:10]([C:12]3[CH:13]=[CH:14][C:15]([C:16]#[N:17])=[CH:18][CH:19]=3)[CH2:9]2)=[O:7])=[CH:4][C:3]=1[C:22]1[NH:26][C:25]([CH:27]2[CH2:32][CH2:31][N:30]([CH3:34])[CH2:29][CH2:28]2)=[N:24][C:23]=1[CH3:33]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 962WaterHCID 178425785HCID 178425785, compound

Product 1

HCID 178425786HCID 178425786, compound

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

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 CH2Cl2, was added trifluoroacetic acid (4 mL). The reaction stirred for 1.5 hours and concentrated under reduced pressure, neutralized with 10 mL Na2CO3 (1M) and lyophilized to afford 4-(1-(4-methyl-3-(4-methyl-2-(piperidin-4-yl)-1H-imidazol-5-yl)benzoyl)azetidin-3-yl)benzonitrile. The mixture of 4-(1-(4-methyl-3-(4-methyl-2-(piperidin-4-yl)-1H-imidazol-5-yl)benzoyl)azetidin-3-yl)benzonitrile (135 mg, 0.31 mmol), formic acid (300 μL, 6.76 mmol), formaldehyde (37% in water, 300 μL, 3.41 mmol) and water (1.5 mL) was heated to reflux for 10 hours. The reaction was diluted with saturated NaHCO3 until pH 9 and extracted with CH2Cl2 (3×20 mL). The residue was purified by preparative TLC with 10% methanol and 1% ammonium hydroxide in dichloromethane and lyophilized to give 43 mg (30% two steps) of the title compound as a white solid. m/z (ES+) 540 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 10 hours
  3. extractionextracted with CH2Cl2 (3×20 mL)
  4. customThe residue was purified by preparative TLC with 10% methanol and 1% ammonium hydroxide in dichloromethane

Sources & evidence

ORD record
ord-6442fc3717ee44fa94d37db6b92695af
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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