Oxalyl chloride → N-[5-[4,4-dimethyl-2,5-dioxo-3-(pyridin-4-ylmethyl)imidazolidin-1-yl]-2-(trifluoromethoxy)phenyl]-1-methylpiperidine-3-carboxamide;2,2,2-trifluoroacetic acid

HRID 2356943Notes

Reaction equation

HRID 2356943 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]([OH:11])=[O:10])[CH2:4]1.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[CH:20]=[C:21]([N:30]2[C:34](=[O:35])[C:33]([CH3:37])([CH3:36])[N:32]([CH2:38][C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)[C:31]2=[O:45])[CH:22]=[CH:23][C:24]=1[O:25][C:26]([F:29])([F:28])[F:27].C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CN(C=O)C>[F:29][C:26]([F:27])([F:28])[C:9]([OH:11])=[O:10].[CH3:36][C:33]1([CH3:37])[C:34](=[O:35])[N:30]([C:21]2[CH:22]=[CH:23][C:24]([O:25][C:26]([F:28])([F:27])[F:29])=[C:19]([NH:18][C:9]([CH:5]3[CH2:6][CH2:7][CH2:8][N:3]([CH3:2])[CH2:4]3)=[O:11])[CH:20]=2)[C:31](=[O:45])[N:32]1[CH2:38][C:39]1[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 125147111-Methylpiperidine-3-carboxylic acid hydrochlorideHCID 231103083-(3-Amino-4-trifluoromethoxyphenyl)5,5-dimethyl-1-pyridin-4-ylmethylimidazolidine-2,4-dione

Product 1

HCID 131728247N-[5-[4,4-dimethyl-2,5-dioxo-3-(pyridin-4-ylmethyl)imidazolidin-1-yl]-2-(trifluoromethoxy)phenyl]-1-methylpiperidine-3-carboxamide;2,2,2-trifluoroacetic acid

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

270 mg (1.50 mmol) 1-methyl-piperidine-3-carboxylic acid hydrochloride were suspended in 20 ml methylene chloride, 216 mg (1.70 mmol) oxalyl chloride follwoed by 11 mg DMF were added and the mixture stirred at RT for 15 h. The solvent was removed by evaporation. To 30 mg (0.15 mmol) of the resulting acid chloride hydrochloride were given a solution of 39 mg (0.10 mmol) 3-(3-amino-4-trifluormethoxy-phenyl)-5,5-dimethyl-1-pyridin-4-ylmethyl-imidazolidine-2,4-dione and 12 mg (0.10 mmol) DMAP in 3 ml methylene chloride. After stirring for 2 h at RT, the mixture was poured on diluted sodium bicarbonate solution, extracted with methylene chloride, then dried and evaporated. The residue was was purified by preparative HPLC. (C18 reversed phase column, elution with a water (0.1% trifluoracetic acid)/acetonitrile gradient) Yield: 8 mg

Workup

  1. additionwere added
  2. customThe solvent was removed by evaporation
  3. stirringAfter stirring for 2 h at RT
  4. extractionextracted with methylene chloride
  5. customdried
  6. customevaporated
  7. customThe residue was was purified by preparative HPLC
  8. washphase column, elution with a water (0.1% trifluoracetic acid)/acetonitrile gradient) Yield: 8 mg

Sources & evidence

ORD record
ord-0f6db42ebee145899ed3f53b1b233d59
Source dataset
uspto-grants-2010_07
Patent number
US07759379B2

Reaction notes

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