Dimethylformamide → Tert-butyl 3-(5-(3-chlorophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate

HRID 624737Notes

Reaction equation

HRID 624737 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=3)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:12]3[N:29]=[CH:30][CH:31]=[C:11]3[N:10]=2)[CH:5]=[CH:6][CH:7]=1.O=P(Cl)(Cl)Cl.CN([CH:40]=[O:41])C>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=3)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:12]3[N:29]=[CH:30][C:31]([CH:40]=[O:41])=[C:11]3[N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 58314302Tert-butyl 3-(5-(3-chlorophenylamino)pyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate

Product 1

HCID 58314670Tert-butyl 3-(5-(3-chlorophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-ylamino)benzoateYield 12%

Procedure

To tert-butyl 3-(5-(3-chlorophenylamino)pyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate (965 mg, 2.2 mmol) in DMF (8.2 mL), POCl3 (1.2 mL, 13.3 mmol) was added dropwise at room temperature. After the addition was complete, the reaction was stirred for 3 days at room temperature. Then, the reaction was quenched by slow addition to ice cold 6N NaOH. The mixture was diluted with water and the solid was collected by filtration. The solid was washed several more times with water then dried under vacuum overnight. The product, tert-butyl 3-(5-(3-chlorophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate, was collected as a solid in 12% yield after purification by column chromatography on silica using 5% acetone/dichloromethane as the eluent. LCMS (M+1=464)

Workup

  1. additionAfter the addition
  2. customThen, the reaction was quenched by slow addition to ice cold 6N NaOH
  3. additionThe mixture was diluted with water
  4. filtrationthe solid was collected by filtration
  5. washThe solid was washed several more times with water
  6. customthen dried under vacuum overnight
  7. customThe product, tert-butyl 3-(5-(3-chlorophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate, was collected as a solid in 12% yield
  8. customafter purification by column chromatography on silica using 5% acetone/dichloromethane as the eluent

Sources & evidence

ORD record
ord-addf1ce49fb9431e821ec8270e6e24d1
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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