Water → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(5,6-dimethyl-pyridine-3-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-one

HRID 226991Notes

Reaction equation

HRID 226991 reaction equation
C([Mg]Cl)(C)C.I[C:7]1[CH:8]=[C:9]([CH3:14])[C:10]([CH3:13])=[N:11][CH:12]=1.CON(C)[C:18]([C:20]1[C:29](=[O:30])[C:28]2[C:23](=[N:24][C:25]([CH3:31])=[CH:26][CH:27]=2)[N:22]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Br:39])[N:34]=2)[CH:21]=1)=[O:19].O>O1CCCC1>[Br:39][C:35]1[N:34]=[C:33]([CH2:32][N:22]2[C:23]3[C:28](=[CH:27][CH:26]=[C:25]([CH3:31])[N:24]=3)[C:29](=[O:30])[C:20]([C:18]([C:7]3[CH:12]=[N:11][C:10]([CH3:13])=[C:9]([CH3:14])[CH:8]=3)=[O:19])=[CH:21]2)[CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 962WaterHCID 206625845-Iodo-2,3-dimethylpyridineHCID 577545251-(6-Bromo-pyridin-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl-amideHCID 178418918HCID 178418918, compound

Product 1

HCID 577546731-(6-Bromo-pyridin-2-ylmethyl)-3-(5,6-dimethyl-pyridine-3-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-oneYield 39.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

0.23 mL (0.469 mmol, 2M in THF) isopropylmagnesium chloride was added to a solution of 104.4 mg (0.448 mmol) of 5-iodo-2,3-dimethyl-pyridine in 1 mL of tetrahydrofuran. After the reaction was stirred for 40 min at room temperature 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 in 0.6 mL of tetrahydrofuran was added and the reaction stirred for 1 h. Water was added and was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and dried in vacuo. The crude product was purified by flash column chromatography using 20-100% ethyl acetate in hexane to yield 37.4 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(5,6-dimethyl-pyridine-3-carbonyl)-7-methyl-1H-[1,8]naphthyridin-4-one. LC-MSD, m/z for C23H19BrN4O2 [M+H]: 463.07 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 1.7 min

Workup

  1. additionwas added
  2. extractionwas extracted with dichloromethane (3×10 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. customdried in vacuo
  6. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-1e80b9e2c3b24ec284979ca967869979
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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