6,7-Dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl amide → 3-(4-Methoxy-3-methyl-benzoyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,8]naphthyridin-4-one

HRID 226999노트

반응식

HRID 226999 반응식
CON(C)[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([CH3:18])=[C:12]([CH3:17])[CH:13]=2)[N:8]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=2)[CH:7]=1)=[O:5].[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([Mg]Br)=[CH:32][C:31]=1[CH3:38]>C1COCC1>[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([C:4]([C:6]2[C:15](=[O:16])[C:14]3[C:9](=[N:10][C:11]([CH3:18])=[C:12]([CH3:17])[CH:13]=3)[N:8]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=3)[CH:7]=2)=[O:5])=[CH:32][C:31]=1[CH3:38]

참가 물질

4

반응물 2

HCID 577545586,7-Dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl amideHCID 178491913HCID 178491913, 화합물

생성물 1

HCID 577547103-(4-Methoxy-3-methyl-benzoyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,8]naphthyridin-4-one수율 34.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Experimental conditions analogous to those described for Step 6 of Example 60 were used with 100 mg (0.273 mmol) of 6,7-Dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl amide, 1.2 mL (0.60 mmol, 0.5 M in tetrahydrofuran) of 4-methoxy-3-methylphenylmagnesium bromide and 1.2 mL of THF. The crude product was purified by flash column chromatography using 20-100% ethyl acetate in hexane and further purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA to give 40.1 mg of 3-(4-Methoxy-3-methyl-benzoyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,8]naphthyridin-4-one. LC-MSD, m/z for C26H25N3O3 [M+H]: 428.19 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.2 min.

후처리

  1. customThe crude product was purified by flash column chromatography
  2. customfurther purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA

출처 및 근거

ORD 기록
ord-a6d3152a08024f9db29351f09163ce1a
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557213B2

반응 노트

불러오는 중…