Dichloromethane → N-{5-[7-(1-Ethyl-propyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]-4-methyl-thiophen-2-yl}acetamide

HRID 1639668Notes

Reaction equation

HRID 1639668 reaction equation
[N+:1]([C:4]1[S:8][C:7]([C:9]2[C:10]([CH3:24])=[N:11][N:12]3[C:17]([CH:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[CH:16][C:15]([CH3:23])=[N:14][C:13]=23)=[C:6]([CH3:25])[CH:5]=1)([O-])=O.[C:26](Cl)(=[O:28])[CH3:27].ClCCl>C1COCC1.[Pd]>[CH2:19]([CH:18]([C:17]1[N:12]2[N:11]=[C:10]([CH3:24])[C:9]([C:7]3[S:8][C:4]([NH:1][C:26](=[O:28])[CH3:27])=[CH:5][C:6]=3[CH3:25])=[C:13]2[N:14]=[C:15]([CH3:23])[CH:16]=1)[CH2:21][CH3:22])[CH3:20]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6367Acetyl chlorideHCID 667211283-(5-Nitro-3-methyl-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 66721108N-{5-[7-(1-Ethyl-propyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]-4-methyl-thiophen-2-yl}acetamideYield 26%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 3-(5-nitro-3-methyl-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.33 g, 0.92 mmol) in THF (10 mL) with 10% palladium on carbon (0.10 g), degas with vacuum/hydrogen atmosphere flush (3×) and stir under a hydrogen atmosphere (55 psi) at room temperature for 3 h. Confirm the reaction is complete using TLC. Dilute the reaction with THF (50 mL) and filter through diatomaceous earth, followed by concentration to a crude orange oil (0.328 g). Dissolve the oil in dichloromethane (4 mL) and 1.0 M NaOH (1 mL). Add acetyl chloride (0.038 mL, 0.52 mmol) to the reaction and stir in a sealed reaction vessel at room temperature over the weekend. Dilute the reaction with dichloromethane (100 mL) and wash with water. Collect the organic phase, dry over anhydrous magnesium sulfate, filter, and concentrate to a red oil under reduced pressure. Purify the oil using flash chromatography, eluting with 100% hexane/0% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) to 0% hexane/100% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) in a step gradient of 10% increments to give a brown foam (0.048 g, 26%). ES/MS m/z 371.0 (M+1)+.

Workup

  1. customdegas with vacuum/hydrogen atmosphere
  2. customflush (3×)
  3. additionDilute
  4. customthe reaction with THF (50 mL)
  5. filtrationfilter through diatomaceous earth
  6. concentrationfollowed by concentration to a crude orange oil (0.328 g)
  7. dissolutionDissolve the oil in dichloromethane (4 mL)
  8. stirringstir in a sealed reaction vessel at room temperature over the weekend
  9. additionDilute
  10. washwash with water
  11. customCollect the organic phase
  12. dry with materialdry over anhydrous magnesium sulfate
  13. filtrationfilter
  14. concentrationconcentrate to a red oil under reduced pressure
  15. customPurify the oil
  16. washeluting with 100% hexane/0% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) to 0% hexane/100% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) in a step gradient of 10% increments

Sources & evidence

ORD record
ord-b7d6d0c45749436bb8ab466796bdac46
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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