Methyl iodide → N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methyl-2-piperidyl)-6-oxo-pyrimidine-4-carboxamide

HRID 1351351Notes

Reaction equation

HRID 1351351 reaction equation
C([O:9][C:10]1[C:15](=[O:16])[N:14]([CH3:17])[C:13]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][NH:19]2)=[N:12][C:11]=1[C:24]([O:26]C)=O)(=O)C1C=CC=CC=1.[CH2:28](OC(N1CCCCC1C(O)=O)=O)C1C=CC=CC=1.C(N(CC)CC)C.CI.[F:56][C:57]1[CH:64]=[CH:63][C:60]([CH2:61][NH2:62])=[CH:59][CH:58]=1>C(#N)C.O>[F:56][C:57]1[CH:64]=[CH:63][C:60]([CH2:61][NH:62][C:24]([C:11]2[N:12]=[C:13]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][N:19]3[CH3:28])[N:14]([CH3:17])[C:15](=[O:16])[C:10]=2[OH:9])=[O:26])=[CH:59][CH:58]=1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 44310261-Carbobenzoxy-2-piperidinecarboxylic AcidHCID 17961843Methyl 5-(benzoyloxy)-1-methyl-6-oxo-2-piperidin-2-yl-1,6-dihydropyrimidine-4-carboxylate

Product 1

HCID 54677580N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methyl-2-piperidyl)-6-oxo-pyrimidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Methyl 5-(benzoyloxy)-1-methyl-6-oxo-2-piperidin-2-yl-1,6-dihydropyrimidine-4-carboxylate (prepared from 1-(benzyloxycarbonyl)piperidine-2-carboxylic acid by procedures similar to those set forth in Examples 1 or 2 in combination with a deprotection step) was suspended in TiF and treated with 3 eq. of triethylamine and 3 eq. of methyl iodide at 40° C. After stirring for 5 h, THF was evaporated and residue poured into EtOAc and washed with brine. Organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The oily residue was taken into EtOAc and treated with 3 eq. of 4-fluorobenzylamine at 90° C. for 0.5 h. The title product was isolated as its trifluoroacetic salt by preparative RP-HPLC (C18, 5 μM, acetonitrile/water containing 0.1% TFA as eluant).

Workup

  1. customTHF was evaporated
  2. additionresidue poured into EtOAc
  3. washwashed with brine
  4. dry with materialOrganic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-81f6bf256b1b47d0a4233738fe3b01fb
Source dataset
uspto-grants-2007_05
Patent number
US07217713B2

Reaction notes

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