Hydrochloric Acid → HCID 58196600, compound

HRID 624767Notes

Reaction equation

HRID 624767 reaction equation
[CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[CH:12][CH:13]=[C:9]3[N:8]=[C:7]([S:14][CH3:15])[N:6]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].Cl.CN([CH:27]=[O:28])C>>[CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[CH:12][C:13]([CH:27]=[O:28])=[C:9]3[N:8]=[C:7]([S:14][CH3:15])[N:6]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 14798Sodium Hydroxide2×HCID 24813Phosphorus oxychlorideHCID 58196429HCID 58196429, compound

Product 1

HCID 58196600HCID 58196600, compound

Conditions

Temperature
70 °C

Procedure

N-Cyclopropyl-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazin-4-amine (1.0 eq, 3.10 g, 14.00 mmol) was dissolved in anhydrous DMF (50 ml) under nitrogen atmosphere. Phosphorus oxychloride (5.0 eq, 6.4 ml, 69.9 mmol) was added dropwise over 5 minutes. Internal temperature rose to 45° C. The reaction was stirred in an oil bath at 70° C. for 4.5 hours. The mixture was cooled down and added dropwise into a solution of 6N NaOH (150 ml) chilled with an ice bath. The rate of addition was adjusted to maintain the internal temperature of the aqueous NaOH below 16° C. At the end of the addition, the mixture was neutralized by slow addition of 6N HCl to reach pH=5-6. The resulting solid was filtered, washed with water and dried in a vacuum oven overnight. 4-(cyclopropylamino)-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine-8-carbaldehyde was isolated as tan solid (9.26 g, 93%). LCMS (ES): >95% pure, m/z 250 [M+H]+.

Workup

  1. customrose to 45° C
  2. temperatureThe mixture was cooled down
  3. temperaturechilled with an ice bath
  4. additionThe rate of addition
  5. additionAt the end of the addition
  6. filtrationThe resulting solid was filtered
  7. washwashed with water
  8. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-8d83a5813c4d4c4281b321fb509dfc0b
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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