Ammonium Chloride → 7-(1-Ethyl-propyl)-3-(2-iodo-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660740Notes

Reaction equation

HRID 1660740 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([CH:11]([C:14]1[N:19]2[N:20]=[C:21]([CH3:28])[C:22]([C:23]3[S:27][CH:26]=[N:25][CH:24]=3)=[C:18]2[N:17]=[C:16]([CH3:29])[CH:15]=1)[CH2:12][CH3:13])[CH3:10].[I:30]N1C(=O)CCC1=O.[Cl-].[NH4+]>C1COCC1>[CH2:9]([CH:11]([C:14]1[N:19]2[N:20]=[C:21]([CH3:28])[C:22]([C:23]3[S:27][C:26]([I:30])=[N:25][CH:24]=3)=[C:18]2[N:17]=[C:16]([CH3:29])[CH:15]=1)[CH2:12][CH3:13])[CH3:10]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 120273N-IodosuccinimideHCID 2724682Lithium diisopropylamideHCID 674299217-(1-Ethyl-propyl)-2,5-dimethyl-3-thiazol-5-yl-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 674287187-(1-Ethyl-propyl)-3-(2-iodo-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Add a freshly prepared solution of lithium di-i-propylamide (150 ml; 62 4 mmol, 0.6 M in THF) to a mixture of 7-(1-ethyl-propyl)-2,5-dimethyl-3-thiazol-5-yl-pyrazolo[1,5-a]pyrimidine, (17.8 g, 62 4 mmol) in THF (100 mL) at −78° C. under a nitrogen atmosphere, keeping the temperature below −74° C. during the addition. Stir the mixture at −78° C. for one hour and then add a solution of N-iodosuccinimide (15 g, 63 mmol) in THF (100 mL) keeping temperature below −74° C. Warm the reaction gradually to 22° C. and then add a 10% aqueous solution of ammonium chloride (300 mL). Separate the organic layer and wash the aqueous layer with methyl-t-butyl ether (2×200 mL). Combine the organic layers, dry over sodium sulfate, filter, and evaporate the solvent. Purify the resulting residue by silica gel chromatography, eluting with hexanes/acetone (5/1) to afford the title compound (15 g, 60%). ES/MS m/z 427 (M+1)+.

Workup

  1. customthe temperature below −74° C.
  2. additionduring the addition
  3. customtemperature below −74° C
  4. temperatureWarm
  5. customthe reaction gradually to 22° C.
  6. customSeparate the organic layer
  7. washwash the aqueous layer with methyl-t-butyl ether (2×200 mL)
  8. dry with materialCombine the organic layers, dry over sodium sulfate
  9. filtrationfilter
  10. customevaporate the solvent
  11. customPurify the resulting residue by silica gel chromatography
  12. washeluting with hexanes/acetone (5/1)

Sources & evidence

ORD record
ord-6be71557092b4cb98078b6743b1f64b5
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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