Morpholine → 4-(4-Chloro-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazol-2-yl)morpholine

HRID 1044663Notes

Reaction equation

HRID 1044663 reaction equation
[CH2:1]([CH:3]([C:6]1[N:11]2[N:12]=[C:13]([CH3:22])[C:14]([C:15]3[S:19][C:18](Cl)=[N:17][C:16]=3[Cl:21])=[C:10]2[N:9]=[C:8]([CH3:23])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>O>[CH2:1]([CH:3]([C:6]1[N:11]2[N:12]=[C:13]([CH3:22])[C:14]([C:15]3[S:19][C:18]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[N:17][C:16]=3[Cl:21])=[C:10]2[N:9]=[C:8]([CH3:23])[CH:7]=1)[CH2:4][CH3:5])[CH3:2]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 452757037-(1-Ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 248989774-(4-Chloro-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazol-2-yl)morpholineYield 90.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Charge 7-(1-ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.37 g, 1.00 mmoles), K2CO3 (0.28 g, 2.00 mmoles) and anhydrous morpholine (3 mL) to a round bottom flask equipped with a magnetic stir bar and N2 inlet. Stir the yellow mixture at 100° C. for about 4 hr., during which time the reaction becomes homogeneous. Cool the reaction mixture to room temperature, add H2O (10 mL) and stir the heterogeneous reaction mixture overnight at room temperature. Collected the yellow solid by filtration, wash with H2O and allowed to air dry overnight to give the crude title compound (391 mg). Recrystallize from isopropyl alcohol (3 mL) to yield the title compound as a light yellow crystalline solid (380 mg, 90.6% yield, >99% by LC). MS (ES)=420 (M+1). 1H NMR (CDCl3)=6.45 (1H, s); 3.81 (m, 4H); 3.62 (1H, m); 3.50 (m, 4H); 2.6 (3H, s); 2.45 (3H, s); 1.85 (4H, m); 0.9 (6H, t).

Workup

  1. customequipped with a magnetic stir bar and N2 inlet
  2. temperatureCool the reaction mixture to room temperature
  3. stirringstir the heterogeneous reaction mixture overnight at room temperature
  4. customCollected the yellow solid
  5. filtrationby filtration
  6. washwash with H2O
  7. customto air dry overnight
  8. customto give the crude title compound (391 mg)
  9. customRecrystallize from isopropyl alcohol (3 mL)

Sources & evidence

ORD record
ord-f188e0e1f8f64aebb16feddbaa1cfac0
Source dataset
uspto-grants-2013_10
Patent number
US08563718B2

Reaction notes

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