Hydrochloric Acid → 2-[4-(1-Azido-1-methylethyl)phenyl]-5-methoxy-3-(2-thienyl)-1,6-naphthyridine

HRID 732873Notes

Reaction equation

HRID 732873 reaction equation
[CH3:1][O-:2].[Na+].[N:4]([C:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=O)[CH2:17][C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[CH:12][CH:11]=1)([CH3:9])[CH3:8])=[N+:5]=[N-:6].Cl[C:25]1[C:30]([CH:31]=O)=[C:29]([NH:33]C(=O)OC(C)(C)C)[CH:28]=[CH:27][N:26]=1.Cl>CO.CCOC(C)=O>[N:4]([C:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[C:17]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)=[CH:31][C:30]3[C:29](=[CH:28][CH:27]=[N:26][C:25]=3[O:2][CH3:1])[N:33]=2)=[CH:12][CH:11]=1)([CH3:9])[CH3:8])=[N+:5]=[N-:6]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 52987944tert-Butyl (2-chloro-3-formylpyridin-4-yl)carbamateHCID 866174631-[4-(1-Azido-1-methylethyl)phenyl]-2-(2-thienyl)ethanone

Product 1

HCID 866174642-[4-(1-Azido-1-methylethyl)phenyl]-5-methoxy-3-(2-thienyl)-1,6-naphthyridine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Sodium methoxide (25 weight % in methanol, 0.23 mL) was added to a stirred mixture of 1-[4-(1-azido-1-methylethyl)phenyl]-2-(2-thienyl)ethanone (2-4, 95mg, 0.33mmol) and tert-butyl(2-chloro-3-formylpyridin-4-yl)carbamate (1-3, 100 mg, 0.39 mmol) in methanol (2 mL), then heated to 65° C. for 2 h. The mixture was cooled to rt, diluted with EtOAc, and acidified with 1N HCl. The aqueous was extracted with ethyl acetate and the combined organics were washed with 1:1 brine:water, dried over magnesium sulfate, filtered, and concentrated to give a dark semi-solid. The crude product was purified via automated silica gel chromatography (0-45% EtOAc in hexane with 5% CH2Cl2 over 30 min) to give the title compound as an amber oil. LRMS m/z (M+1) Calcd: 402.2,. Found 402.2.

Workup

  1. temperatureThe mixture was cooled to rt
  2. extractionThe aqueous was extracted with ethyl acetate
  3. washthe combined organics were washed with 1:1 brine
  4. dry with materialwater, dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a dark semi-solid
  8. customThe crude product was purified
  9. customsilica gel chromatography (0-45% EtOAc in hexane with 5% CH2Cl2 over 30 min)

Sources & evidence

ORD record
ord-d240d8f5a40743f795548e85f4ee6d1f
Source dataset
uspto-grants-2009_09
Patent number
US07589068B2

Reaction notes

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