Triethylamine → N-[[3-fluoro-4-(2-hydroxyethoxymethyl)phenyl]methyl]-2-methyl-1,8-naphthyridine-3-carboxamide

HRID 929374Notes

Reaction equation

HRID 929374 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[C:17]([C:18]([OH:20])=O)=[CH:16][C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.C(N(CC)CC)C.[NH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][O:37][CH2:38][CH2:39][OH:40])=[C:32]([F:41])[CH:31]=1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.O>[F:41][C:32]1[CH:31]=[C:30]([CH2:29][NH:28][C:18]([C:17]2[C:8]([CH3:7])=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][N:11]=3)=[O:20])[CH:35]=[CH:34][C:33]=1[CH2:36][O:37][CH2:38][CH2:39][OH:40]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27369082-methyl-1,8-naphthyridine-3-carboxylic acidHCID 28413948HCID 28413948, compound

Product 1

HCID 89647281N-[[3-fluoro-4-(2-hydroxyethoxymethyl)phenyl]methyl]-2-methyl-1,8-naphthyridine-3-carboxamideYield 36.1%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

45 μl oxalyl chloride (0.53 mmol) was added to a mixture of 50 mg 2-methyl-1,8-naphthyridine-3-carboxylic acid (0.27 mmol) in 3 ml CH2Cl2 with one drop DMF. The reaction mixture was stirred for 1.5 h and then evaporated to dryness under reduced pressure. The residue was dissolved in 3 ml CH2Cl2. 4 mg DMAP (0.03 mmol) and 188 μl triethyl amine (1.35 mmol) were added to the solution followed by 54 mg 2-[[4-(aminomethyl)-2-fluoro-phenyl]methoxy]ethanol (0.27 mmol). The reaction mixture was stirred for 4 h and then diluted with water. The phases were separated and the aqueous phase was extracted with CH2Cl2. The combined organic phases were dried (MgSO4) and concentrated. Flash chromatography (SiO2, CH2Cl2/MeOH 20:1) gave 36 mg (36%) of the title compound.

Workup

  1. customevaporated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in 3 ml CH2Cl2
  3. stirringThe reaction mixture was stirred for 4 h
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with CH2Cl2
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ad53874ba60145e28f6f4974a006b7b5
Source dataset
uspto-grants-2016_03
Patent number
US09295738B2

Reaction notes

Loading…