Dichloromethane → {6-[2-(4-Amino-6-methoxy-[1,5]naphthyridin-3-yloxy)-acetyl]-pyridin-3-yl}-carbamic acid tert-butyl ester

HRID 1422925Notes

Reaction equation

HRID 1422925 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12](=[O:24])[NH:13][C:14]1[CH:15]=[N:16][C:17]([C:20](=[O:23])[CH2:21]Br)=[CH:18][CH:19]=1)([CH3:10])([CH3:9])[CH3:8].[NH2:25][C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[N:34]=2)[N:29]=[CH:28][C:27]=1[OH:38].ClCCl>CN(C)C=O.CO>[C:7]([O:11][C:12](=[O:24])[NH:13][C:14]1[CH:15]=[N:16][C:17]([C:20](=[O:23])[CH2:21][O:38][C:27]2[CH:28]=[N:29][C:30]3[C:35]([C:26]=2[NH2:25])=[N:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)=[CH:18][CH:19]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 86671533tert-butyl N-[6-(2-bromoacetyl)pyridin-3-yl]carbamateHCID 1363447124-Amino-6-methoxy-[1,5]naphthyridin-3-ol

Product 1

HCID 67248964{6-[2-(4-Amino-6-methoxy-[1,5]naphthyridin-3-yloxy)-acetyl]-pyridin-3-yl}-carbamic acid tert-butyl esterYield 30.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (140 mg, 1.02 mmol, 1.5 eq) is added at room temperature to a stirred solution of [6-(2-bromo-acetyl)-pyridin-3-yl]-carbamic acid tert-butyl ester (220 mg, 0.70 mmol, 1.0 eq) and 4-amino-6-methoxy-[1,5]naphthyridin-3-ol (130 mg, 0.69 mmol, 1.0 eq) in N,N-dimethylformamide (10 mL). After 30 minutes stirring at room temperature, solvent is removed and the residue is extracted with ethyl acetate (3×15 mL) and water (10 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give the crude product that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 100:1, v/v) to afford {6-[2-(4-amino-6-methoxy-[1,5]naphthyridin-3-yloxy)-acetyl]-pyridin-3-yl}-carbamic acid tert-butyl ester as a red-brown solid (90 mg, 24% yield).

Workup

  1. customsolvent is removed
  2. extractionthe residue is extracted with ethyl acetate (3×15 mL) and water (10 mL)
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product that
  8. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-ed0af7d89c6b41388ea13149b7770344
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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