Dimethylformamide → 5-(5-Chloro-2-fluorophenylamino)-7-(2-morpholinopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

HRID 2037042Notes

Reaction equation

HRID 2037042 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH2:16][CH:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH3:18])[N:12]3[N:25]=[CH:26][CH:27]=[C:11]3[N:10]=2)[CH:7]=1.P(Cl)(Cl)(Cl)=O.CN([CH:37]=[O:38])C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH2:16][CH:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[CH3:18])[N:12]3[N:25]=[CH:26][C:27]([CH:37]=[O:38])=[C:11]3[N:10]=2)[CH:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 58314469HCID 58314469, compound

Product 1

HCID 583140035-(5-Chloro-2-fluorophenylamino)-7-(2-morpholinopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehydeYield 41%

Procedure

In a reaction flask, N5-(5-chloro-2-fluorophenyl)-N7-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine (84 mg, 0.21 mmol) was dissolved in DMF (0.9 mL) then phosphorous oxychloride (58 uL, 0.62 mmol) was added slowly at room temperature. The reaction mixture was allowed to stir at room temperature for 2 days then quenched by addition to 6N NaOH solution. The pH of the mixture was adjusted with 6N HCl to pH=7-9. The solid was recovered by filtration and washed with water. The product, 5-(5-chloro-2-fluorophenylamino)-7-(2-morpholinopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde, was purified by preparative TLC (5% acetone/dichloromethane) to yield 37 mg of the desired product (41% yield). LCMS (M+1=433)

Workup

  1. customthen quenched by addition to 6N NaOH solution
  2. filtrationThe solid was recovered by filtration
  3. washwashed with water
  4. customThe product, 5-(5-chloro-2-fluorophenylamino)-7-(2-morpholinopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde, was purified by preparative TLC (5% acetone/dichloromethane)

Sources & evidence

ORD record
ord-fe85ac5b30654090b59730985b14be45
Source dataset
uspto-grants-2013_11
Patent number
US08575177B2

Reaction notes

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