Sodium bis(trimethylsilyl)amide → 9-bromo-1-butoxy-3-methylbenzo[c]-1,6-naphthyridin-6(5H)-one

HRID 2193002Notes

Reaction equation

HRID 2193002 reaction equation
N[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([O:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:3]=1[C:14]1[CH:28]=[C:27]([Br:29])[CH:26]=[CH:25][C:15]=1[C:16]([N:18](C(C)C)C(C)C)=[O:17].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Br:29][C:27]1[CH:26]=[CH:25][C:15]2[C:16](=[O:17])[NH:18][C:2]3[C:3]([C:14]=2[CH:28]=1)=[C:4]([O:9][CH2:10][CH2:11][CH2:12][CH3:13])[N:5]=[C:6]([CH3:8])[CH:7]=3

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 593754382-(4-amino-2-butoxy-6-methylpyridin-3-yl)-4-bromo-N,N-diisopropylbenzamide

Product 1

HCID 593755699-bromo-1-butoxy-3-methylbenzo[c]-1,6-naphthyridin-6(5H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-(4-amino-2-butoxy-6-methylpyridin-3-yl)-4-bromo-N,N-diisopropylbenzamide (50 mg, 0.10 mmol) in THF (50 mL) was added dropwise a solution of NaHMDS in THF (0.40 mL, 0.20 mmol) at room temperature over 1 h. The resulting mixture was quenched with saturated aqueous NH4Cl solution (3 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (5 mL), dried over magnesium sulfate, filtered and concentrated to afford a crude solid. The crude material was triturated with diethyl ether (5 mL) and filtered to afford 9-bromo-1-butoxy-3-methylbenzo[c]-1,6-naphthyridin-6(5H)-one. 1H-NMR (300 MHz, DMSO) δ 9.13 (d, J=5.7 Hz, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.47 (dd, J1=8.4 Hz, J2=1.8 Hz, 1H), 4.41 (t, J=6.3 Hz, 2H), 2.27 (s, 3H), 1.82 (m, 2H), 1.60 (m, 2H), 1.00 (t, J=7.5 Hz, 3H). LRMS calc'd for (C17H17BrN2O2) [M+H]+, 361; found 362.

Workup

  1. customThe resulting mixture was quenched with saturated aqueous NH4Cl solution (3 mL)
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organic layers were washed with brine (5 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a crude solid
  8. customThe crude material was triturated with diethyl ether (5 mL)
  9. filtrationfiltered

Sources & evidence

ORD record
ord-a50be74ee3514ef4919693c1de73a010
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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