Potassium Carbonate → 2-Amino-6-{[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitrile

HRID 508182Notes

Reaction equation

HRID 508182 reaction equation
[NH2:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][OH:20])=[CH:13][CH:12]=2)[C:3]=1[C:21]#[N:22].Cl[CH2:24][C:25]1[N:26]=[C:27]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[O:28][C:29]=1[CH3:30].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[C:3]([C:21]#[N:22])=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][OH:20])=[CH:13][CH:12]=2)[C:5]([C:9]#[N:10])=[C:6]([O:8][CH2:24][C:25]2[N:26]=[C:27]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[O:28][C:29]=2[CH3:30])[N:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 106092554-(Chloromethyl)-2-(4-fluorophenyl)-5-methyl-1,3-oxazoleHCID 672161816-Amino-4-[4-(2-hydroxyethoxy)phenyl]-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile

Product 1

HCID 672153992-Amino-6-{[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

250 mg (0.81 mmol) of the compound from Example 102A, 228 mg (1.013 mmol) of 4-(chloromethyl)-2-(4-fluorophenyl)-5-methyl-1,3-oxazole and 224 mg (1.62 mmol) of potassium carbonate are initially charged in 8.6 ml of dry DMF and stirred at 70° C. for 2 h. The solvent is then removed on a rotary evaporator and the residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). The product is then purified once more by HPLC (column: Waters Sunfire C 18 5 nm, 250 mm×20 mm; mobile phase gradient: water/ethanol 55:45→5:95; flow rate: 25 ml/min; temperature: 30° C.; detection: 210 nm).

Workup

  1. customThe solvent is then removed on a rotary evaporator
  2. customthe residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)
  3. customThe product is then purified once more by HPLC (column: Waters Sunfire C 18 5 nm, 250 mm×20 mm; mobile phase gradient: water/ethanol 55:45→5:95; flow rate: 25 ml/min; temperature: 30° C.; detection: 210 nm)

Sources & evidence

ORD record
ord-11df4b82745b4dc68b116d4fff5b34a2
Source dataset
uspto-grants-2015_08
Patent number
US09095582B2

Reaction notes

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