Sodium methanolate methanol → 2-[4-(1,3-Dioxolan-2-yl)phenyl]-5-methoxy-3-phenyl-1,6-naphthyridine

HRID 604986Notes

Reaction equation

HRID 604986 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12](=O)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1.Cl[C:22]1[C:27]([CH:28]=O)=[C:26]([NH:30]C(=O)OC(C)(C)C)[CH:25]=[CH:24][N:23]=1.[CH3:38][O-:39].[Na+].CO>CO>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:28][C:27]3[C:26](=[CH:25][CH:24]=[N:23][C:22]=3[O:39][CH3:38])[N:30]=2)=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 23694274Sodium methanolate methanolHCID 52987944tert-Butyl (2-chloro-3-formylpyridin-4-yl)carbamateHCID 591643561-(4-(1,3-Dioxolan-2-yl)phenyl)-2-phenylethanone

Product 1

HCID 592646202-[4-(1,3-Dioxolan-2-yl)phenyl]-5-methoxy-3-phenyl-1,6-naphthyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a partial solution of 1-[4-(1,3-dioxolan-2-yl)phenyl]-2-phenylethanone (997 mg, 3.72 mmol) and tert-butyl (2-chloro-3-formylpyridine-4-yl)carbamate (924 mg, 3.6 mmol) in dry methanol (14 mL) was added 25 wt % sodium methoxide/methanol (2.5 mL, 11.4 mmol). The reaction mixture was warmed at 65° C. for four hours. The cooled reaction was concentrated to remove the methanol and the residue was partitioned between water and ethyl acetate. The organic layer was dried (Na2SO4), filtered and evaporated. The residue was triturated with cold ether to give pure 2-[4-(1,3-dioxolan-2-yl)phenyl]-5-methoxy-3-phenyl-1,6-naphthyridine. The mother liquors were purified by chromatography on silica gel and elution with 20-40% ethyl acetate/hexane gave additional product. 1H-NMR (500 MHz, CDCl3): δ 8.54 (1H, s), 8.23 (1H, d, J=5.9 Hz), 7.55 (1H, d, J=5.9 Hz), 7.48 (2H, d, J=8 Hz), 7.40 (2H, d, J=8 Hz), 7.29-7.30 (3H, m), 7.22-7.25 (2H, m), 4.16 (3H, s), 4.02-411 (4H, 2 m). m/e (m+1): 385.1.

Workup

  1. customThe cooled reaction
  2. concentrationwas concentrated
  3. customto remove the methanol
  4. customthe residue was partitioned between water and ethyl acetate
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was triturated with cold ether

Sources & evidence

ORD record
ord-c7723005c56a41f2ba9c0b72031f4884
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Reaction notes

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