Triethylamine → N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-phenoxypyrimidine-5-carboxamide

HRID 1501161Notes

Reaction equation

HRID 1501161 reaction equation
[O:1]([C:8]1[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:46][CH2:47][C:48]1[C:49]([OH:56])=[N:50][C:51]([CH3:55])=[CH:52][C:53]=1[CH3:54]>ClCCl>[OH:56][C:49]1[C:48]([CH2:47][NH:46][C:14]([C:11]2[CH:12]=[N:13][C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[N:9][CH:10]=2)=[O:16])=[C:53]([CH3:54])[CH:52]=[C:51]([CH3:55])[N:50]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68555610HCID 68555610, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425236N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-phenoxypyrimidine-5-carboxamideYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-phenoxypyrimidine-5-carboxylic acid (300 mg, 1.4 mmol) in dichloromethane (15.0 mL) was added N-hydroxybenzotriazole (270 mg, 2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (384 mg, 2 mmol), triethylamine (202 mg, 2 mmol). Then the mixture was stirred for 30 minutes, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (270 mg, 2 mmol) was added and the mixture was stirred at room temperature 24 hours. The mixture was washed with water (50 mL), and extracted with dichloromethane (2*50 mL). The combined organic phase was separated, dried over sodium sulphate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, methanol/dichloromethane=1:20, 1% NH3) to afford N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-phenoxypyrimidine-5-carboxamide (200 mg, 46%) as white solid. LRMS (M+H+) m/z: calcd 350.14. found 350. HPLC purity (214 nm): 100%. 1H NMR (300 MHz, CD3OD): δ 8.93 (s, 2H), 7.46-7.16 (m, 5H), 6.10 (s, 1H), 4.48 (s, 2H), 2.35 (s, 3H), 2.24 (s, 3H).

Workup

  1. stirringthe mixture was stirred at room temperature 24 hours
  2. washThe mixture was washed with water (50 mL)
  3. extractionextracted with dichloromethane (2*50 mL)
  4. customThe combined organic phase was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue
  9. customThe residue was purified by column chromatography (silica gel, methanol/dichloromethane=1:20, 1% NH3)

Sources & evidence

ORD record
ord-7c7df58911794c768513216c54302a80
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

Loading…