Triethylamine → 2-(3-((5-Fluoropyrimidin-2-yl)oxy)azetidin-1-yl)-5-(trifluoromethyl)nicotinic acid

HRID 72480Notes

Reaction equation

HRID 72480 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[N:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=2)[CH2:2]1.C(N(CC)CC)C.Cl[C:21]1[N:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:22]=1[C:23]([OH:25])=[O:24]>CO.O1CCCC1>[F:12][C:9]1[CH:10]=[N:11][C:6]([O:5][CH:3]2[CH2:2][N:1]([C:21]3[N:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:26][C:22]=3[C:23]([OH:25])=[O:24])[CH2:4]2)=[N:7][CH:8]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 121402272-Chloro-5-(trifluoromethyl)nicotinic acidHCID 679583852-(Azetidin-3-yloxy)-5-fluoropyrimidine

Product 1

HCID 679588812-(3-((5-Fluoropyrimidin-2-yl)oxy)azetidin-1-yl)-5-(trifluoromethyl)nicotinic acidYield 23.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(azetidin-3-yloxy)-5-fluoropyrimidine (D51) (108 mg, 0.638 mmol) and triethylamine (0.11 ml, 0.798 mmol) in methanol (1 ml) and tetrahydrofuran (2 ml), 2-chloro-5-(trifluoromethyl)nicotinic acid (120 mg, 0.532 mmol) was added and the mixture was heated 2 h at 80° C. After solvent evaporation the residue was purified by SPE-Si cartridge (25 g) eluting with a mixture dichloromethane/methanol from 95/5 to 80/20. Collected fraction after solvent evaporation afforded the title compound (D131) (44 mg)

Workup

  1. additionwas added
  2. customAfter solvent evaporation the residue
  3. customwas purified by SPE-Si cartridge (25 g)
  4. washeluting with a mixture dichloromethane/methanol from 95/5 to 80/20
  5. customCollected fraction
  6. customafter solvent evaporation

Sources & evidence

ORD record
ord-0c696a5e43d84d38bbe2a2bcd7a6111b
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

Loading…