Tetrahydrofuran → 4-Bromo-5-[7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-thiazole-2-carbaldehyde

HRID 1660755Notes

Reaction equation

HRID 1660755 reaction equation
C([Li])CCC.C1C[O:9][CH2:8]C1.Br[C:12]1[S:13][C:14]([C:18]2[C:19]([CH3:33])=[N:20][N:21]3[C:26]([CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[CH:25][C:24]([CH3:32])=[N:23][C:22]=23)=[C:15]([Br:17])[N:16]=1.C(N1CCOCC1)=O>CCOCC>[Br:17][C:15]1[N:16]=[C:12]([CH:8]=[O:9])[S:13][C:14]=1[C:18]1[C:19]([CH3:33])=[N:20][N:21]2[C:26]([CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[CH:25][C:24]([CH3:32])=[N:23][C:22]=12

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 20417N-FormylmorpholineHCID 674295502,4-Dibromo-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazoleHCID 178418339Butyllithium

Product 1

HCID 866450044-Bromo-5-[7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-thiazole-2-carbaldehyde

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Under a nitrogen atmosphere, add n-butyl lithium (1.6 M in hexanes, 0.312 mL, 0.50 mmol) to a THF solution (2.5 mL) of 3-(2,4-dibromo-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (230 mg, 0.50 mmol) at −78° C. and stir for 30 min. Add a THF (0.5 mL) solution of N-formyl morpholine (58 mg, 0.50 mmol). Stir for one hour, then store the reaction at −20° C. overnight. Warm the reaction to room temperature, dilute with ether, and quench by adding 4 N HCl (4 mL). Separate and extract the organic phase with 4 N HCl (2×4 mL). Combine the aqueous portions, treat with solid sodium bicarbonate to pH=8 to 9 and then extract with diethyl ether. Combine all the organic layers, wash with brine, dry over sodium sulfate, filter, and concentrate to a residue. Purify the crude material by flash chromatography, eluting with hexanes/dichloromethane/ethyl acetate (5/5/1) to give the title compound (154 mg). MS (APCI) m/z (81Br) 409.0 (M+1)+.

Workup

  1. stirringStir for one hour
  2. customthe reaction at −20° C. overnight
  3. temperatureWarm
  4. customthe reaction to room temperature
  5. customquench
  6. additionby adding 4 N HCl (4 mL)
  7. customSeparate
  8. extractionextract the organic phase with 4 N HCl (2×4 mL)
  9. additionCombine the aqueous portions, treat with solid sodium bicarbonate to pH=8 to 9
  10. extractionextract with diethyl ether
  11. washwash with brine
  12. dry with materialdry over sodium sulfate
  13. filtrationfilter
  14. concentrationconcentrate to a residue
  15. customPurify the crude material by flash chromatography
  16. washeluting with hexanes/dichloromethane/ethyl acetate (5/5/1)

Sources & evidence

ORD record
ord-6039e6b4261e45aabd188685856a7c44
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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