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

HRID 2114766노트

반응식

HRID 2114766 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-22e95058eb834bceb6acac4d7c5d95d7
출처 데이터셋
uspto-grants-2008_10
특허 번호
US07435734B2

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