Ammonium Chloride → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(2,3-dihydro-benzo[1,4]dioxine-6-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-one

HRID 226989Notes

Reaction equation

HRID 226989 reaction equation
[CH2:1]1[O:10][C:9]2[C:4](=[CH:5][C-:6]=[CH:7][CH:8]=2)[O:3][CH2:2]1.[Mg+2].[Br-].CON(C)[C:16]([C:18]1[C:27](=[O:28])[C:26]2[C:21](=[N:22][C:23]([CH3:29])=[CH:24][CH:25]=2)[N:20]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Br:37])[N:32]=2)[CH:19]=1)=[O:17].[Cl-].[NH4+]>C1COCC1>[Br:37][C:33]1[N:32]=[C:31]([CH2:30][N:20]2[C:21]3[C:26](=[CH:25][CH:24]=[C:23]([CH3:29])[N:22]=3)[C:27](=[O:28])[C:18]([C:16]([C:7]3[CH:6]=[CH:5][C:4]4[O:3][CH2:2][CH2:1][O:10][C:9]=4[CH:8]=3)=[O:17])=[CH:19]2)[CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 15974803Magnesium bromide 2,3-dihydro-1,4-benzodioxin-6-ide (1/1/1)HCID 577545251-(6-Bromo-pyridin-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl-amide

Product 1

HCID 577546501-(6-Bromo-pyridin-2-ylmethyl)-3-(2,3-dihydro-benzo[1,4]dioxine-6-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-oneYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.896 mL of 3,4-(ethylenedioxy)phenylmagnesium bromide (0.448 mmol, 0.5M in THF) was added to 85 mg (0.204 mmol) of 1-(6-Bromo-pyridin-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl-amide dissolved in 1 mL of THF and the reaction was stirred at room temperature for 1 hour. Saturated ammonium chloride was added and the aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. 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 yield 38.2 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(2,3-dihydro-benzo[1,4]dioxine-6-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-one as a white solid. LC-MSD, m/z for C24H18BrN3O4 [M+H]: 492.05 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.4 min

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane (3×10 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography
  6. customfurther purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA

Sources & evidence

ORD record
ord-a08d2ffff1884c6a989638feb88e8375
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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