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

HRID 1660740ノート

反応式

HRID 1660740 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-6be71557092b4cb98078b6743b1f64b5
出典データセット
uspto-grants-2011_10
特許番号
US08030304B2

反応ノート

読み込み中…