Phosphorus oxychloride → HCID 66778025, compound

HRID 406310Notes

Reaction equation

HRID 406310 reaction equation
O=[C:2]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][N:9]2[N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]4)=[C:18]([O:28][CH3:29])[N:17]=3)[N:15]=[C:8]12)=[O:6].C(Cl)(=O)C(Cl)=O.P(Cl)(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH3:29][O:28][C:18]1[N:17]=[C:16]([C:14]2[N:15]=[C:8]3[CH:7]([C:5]4[O:6][C:2]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)=[CH:3][N:4]=4)[CH2:12][CH2:11][CH2:10][N:9]3[N:13]=2)[CH:21]=[CH:20][C:19]=1[N:22]1[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]1

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 66618765HCID 66618765, compound

Product 1

HCID 66778025HCID 66778025, compoundYield 12.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6212ChloroformSolvent

Procedure

2-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine-8-carboxylic acid (2-oxo-2-phenylethyl)amide obtained in Example 172 (35.7 mg) was suspended in toluene (0.5 mL). Oxalyl chloride (20.4 mg) was added and the mixture was stirred with heating under reflux for two hours. Toluene (3 mL) and phosphoryl chloride (60 μL) were added, followed by further stirring for two hours and 30 minutes. The reaction solution was ice-cooled. Then, chloroform and a saturated sodium bicarbonate solution were added and the organic layer was separated. The resulting organic layer was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography to obtain the title compound (4.4 mg). The compound was further purified by CHIRALPAK™ IA (2 cm×25 cm; mobile phase:hexane:ethanol=50:50) to obtain the title compound (1.2 mg, racemate). The property values of the compound are as follows.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for two hours
  3. stirringby further stirring for two hours and 30 minutes
  4. temperaturecooled
  5. customthe organic layer was separated
  6. concentrationThe resulting organic layer was concentrated under reduced pressure
  7. customThe residue was purified by NH silica gel column chromatography

Sources & evidence

ORD record
ord-34b23300726149dfa24ed486466ae733
Source dataset
uspto-grants-2014_06
Patent number
US08754100B2

Reaction notes

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