Sodium borohydride → N-(8-chloro-6-methyl-5,6-dihydrobenzo[c][2,7]naphthyridin-2-yl)acetamide

HRID 1398354Notes

Reaction equation

HRID 1398354 reaction equation
[F-].[C:2]([NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][N:15]=1)[CH:12]=[N+:11]([CH3:16])[C:10]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:9]2=1)(=[O:4])[CH3:3].[BH4-].[Na+]>C1COCC1.CO>[Cl:21][C:18]1[CH:19]=[CH:20][C:9]2[C:8]3[C:13](=[CH:14][N:15]=[C:6]([NH:5][C:2](=[O:4])[CH3:3])[CH:7]=3)[CH2:12][N:11]([CH3:16])[C:10]=2[CH:17]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 867103462-Acetamido-8-chloro-6-methylbenzo[c][2,7]naphthyridin-6-ium fluoride

Product 1

HCID 86710348N-(8-chloro-6-methyl-5,6-dihydrobenzo[c][2,7]naphthyridin-2-yl)acetamideYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-acetamido-8-chloro-6-methylbenzo[c][2,7]naphthyridin-6-ium fluoride (2.1 g, 2.47 mmol) in a mixture of THF (20 mL) and MeOH (5 mL) at 0° C. was added NaBH4 (0.199 g, 5.27 mmol) in three portions and the reaction was stirred at rt for 45 min. The volatile organics were removed under reduced pressure; saturated ammonium chloride solution (30 mL) was added and the solution extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with brine (25 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford N-(8-chloro-6-methyl-5,6-dihydrobenzo[c][2,7]naphthyridin-2-yl)acetamide (0.71 g, 2.29 mmol, 93% yield) as a yellow solid. LC/MS (ESI) m/e 288.2 [(M+H)+, calcd for C15H15ClN3O 288.1]; LC/MS retention time (method C); tR=1.87 min; HPLC retention time (method A): tR=12.76 min; HPLC retention time (method B): tR=13.07 min; 1H NMR (400 MHz, DMSO-d6) δ 10.46 (s, 1H), 8.36 (s, 1H), 8.16 (d, J=0.40 Hz, 1H), 7.63 (d, J=8.40 Hz, 1H), 6.88 (dd, J=2.00, 8.00 Hz, 1H), 6.82 (d, J=2.00 Hz, 1H), 4.26 (s, 2H), 2.89 (s, 3H), 2.11 (s, 3H).

Workup

  1. customThe volatile organics were removed under reduced pressure
  2. additionsaturated ammonium chloride solution (30 mL) was added
  3. extractionthe solution extracted with ethyl acetate (2×30 mL)
  4. washThe combined organic layers were washed with brine (25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2f83b7ee7e4d457f839cf6b2026bbe39
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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