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Nitrogen → 7-(1-Ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1044662
Notes
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Reaction equation

HRID 1044662 reaction equation
[CH2:1]([CH:3]([C:6]1[N:11]2[N:12]=[C:13]([CH3:16])[C:14](I)=[C:10]2[N:9]=[C:8]([CH3:17])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:26][C:27]1[S:28][CH:29]=[C:30]([Cl:32])[N:31]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.N#N>[Cu]I.CC(N(C)C)=O>[CH2:1]([CH:3]([C:6]1[N:11]2[N:12]=[C:13]([CH3:16])[C:14]([C:29]3[S:28][C:27]([Cl:26])=[N:31][C:30]=3[Cl:32])=[C:10]2[N:9]=[C:8]([CH3:17])[CH:7]=1)[CH2:4][CH3:5])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 947NitrogenHCID 13181,10-PhenanthrolineHCID 62657Potassium Phosphate, TribasicHCID 123331552,4-DichlorothiazoleHCID 248985233-Iodo-2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 45275703
7-(1-Ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine
Yield 70%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Charge 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (1.03 g, 3.00 mmoles), K3PO4 (1.95 g, 9.00 mmoles), 2,4-dichlorothiazole (0.58 g, 3.75 mmoles), 1,10 phenanthroline (0.05 g, 0.30 mmoles) and anhydrous DMAC (5 mL) to a round bottom flask equipped with a magnetic stir bar, thermal couple and N2 inlet. Degas the yellow heterogeneous reaction mixture with N2 (gas) for 30 min. and then add CuI (0.06 g, 0.30 mmoles) in one portion followed by additional 30 min. degassing with N2 (gas). Stir the reaction mixture at 120° C. for about 6 hr. Cool the reaction mixture to room temperature overnight, add toluene (10 mL) and stir for 1 hr. Purify the mixture through silica gel eluting with toluene (10 ml). Extract with 1 M HCl (10 mL), water (10 mL), brine (10 mL) and concentrate under reduced pressure to give a yellow solid. Recrystallize the solid from methanol (5 ml) to yield the title compound as a yellow crystalline solid. (0.78 g, 70% yield, >99% pure by LC) MS (ES)=369 (M+1). 1H NMR (CDCl3)=6.5 (1H, s); 3.6 (1H, m); 2.6 (3H, s); 2.5 (3H, s); 1.9 (4H, m); 0.9 (6H, t).

Workup

  1. customequipped with a magnetic stir bar
  2. customDegas the yellow heterogeneous reaction mixture with N2 (gas) for 30 min.
  3. customdegassing with N2 (gas)
  4. temperatureCool the reaction mixture to room temperature overnight
  5. additionadd toluene (10 mL)
  6. stirringstir for 1 hr
  7. customPurify the mixture through silica gel eluting with toluene (10 ml)
  8. extractionExtract with 1 M HCl (10 mL), water (10 mL), brine (10 mL)
  9. concentrationconcentrate under reduced pressure
  10. customto give a yellow solid
  11. customRecrystallize the solid from methanol (5 ml)

Sources & evidence

ORD record
ord-e81da3655835453dae1e8e6d9352def3
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08563718B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes