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

HRID 2114766Notes

Reaction equation

HRID 2114766 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>C1COCC1.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

8

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 2

HCID 8028TetrahydrofuranSolventHCID 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 THF 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-22e95058eb834bceb6acac4d7c5d95d7
Source dataset
uspto-grants-2008_10
Patent number
US07435734B2

Reaction notes

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