Magnesium bromide 2,3-dihydro-1,4-benzodioxin-6-ide (1/1/1) → 3-(2,3-Dihydro-benzo[1,4]dioxine-6-carbonyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1h-[1,8]naphthyridin-4-one

HRID 226998Notes

Reaction equation

HRID 226998 reaction equation
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].[CH2:28]1[O:37][C:36]2[C:31](=[CH:32][C-:33]=[CH:34][CH:35]=2)[O:30][CH2:29]1.[Mg+2].[Br-]>C1COCC1>[O:30]1[C:31]2[CH:32]=[CH:33][C:34]([C:4]([C:6]3[C:15](=[O:16])[C:14]4[C:9](=[N:10][C:11]([CH3:18])=[C:12]([CH3:17])[CH:13]=4)[N:8]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=4)[CH:7]=3)=[O:5])=[CH:35][C:36]=2[O:37][CH2:28][CH2:29]1

Participants

4

Reactant 2

HCID 15974803Magnesium bromide 2,3-dihydro-1,4-benzodioxin-6-ide (1/1/1)HCID 577545586,7-Dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl amide

Product 1

HCID 577547883-(2,3-Dihydro-benzo[1,4]dioxine-6-carbonyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1h-[1,8]naphthyridin-4-oneYield 35.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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, 0.5M solution in tetrahydrofuran) of 3,4-(ethylenedioxy)phenylmagnesium bromide, and 1 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 afford 42.7 mg of 3-(2,3-Dihydro-benzo[1,4]dioxine-6-carbonyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,8]naphthyridin-4-one. LC-MSD, m/z for C26H23N3O4 [M+H]: 442.17 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 1.9 min.

Workup

  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

Sources & evidence

ORD record
ord-841108da592d447482367d94963954b4
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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