Thionyl Chloride → 2-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carbonyl azide

HRID 877557Notes

Reaction equation

HRID 877557 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([C:13](O)=[O:14])[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1.S(Cl)(Cl)=O.[N-:25]=[N+:26]=[N-:27].[Na+]>O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([C:13]([N:25]=[N+:26]=[N-:27])=[O:14])[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 896897472-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylic acid

Product 1

HCID 896898232-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carbonyl azide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylic acid (30a) (750 mg, 2.54 mmol) and thionyl chloride (12.68 mmol) were refluxed at 100° C. for 20 h. Thionyl chloride was removed under reduced pressure. The resulting solid acid chloride was dissolved in acetone (15 mL) and cooled to 0° C. Sodium azide (7.61 mmol) dissolved in water (3 mL) was added to the reaction mixture at 0° C. and stirred for 30 min. The reaction temperature was raised to room temperature and stirred for 5 h. The reaction mixture was concentrated to remove the solvent. The compound precipitated in the aqueous layer was filtered and dried under vacuum to obtain the desired compound 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carbonyl azide. LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 2.363 min.

Workup

  1. customThionyl chloride was removed under reduced pressure
  2. dissolutionThe resulting solid acid chloride was dissolved in acetone (15 mL)
  3. additionwas added to the reaction mixture at 0° C.
  4. temperatureThe reaction temperature was raised to room temperature
  5. stirringstirred for 5 h
  6. concentrationThe reaction mixture was concentrated
  7. customto remove the solvent
  8. customThe compound precipitated in the aqueous layer
  9. filtrationwas filtered
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5171aea5bed24f12ab6c37df0a5ff915
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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