Lithium Hydroxide → 2-tert-Butyl-4-{4-[3-(4-methyl-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclopropyl-pyrimidine hydrochloride

HRID 219750노트

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HRID 219750 반응식
[CH3:1][N:2]1[C:6]([CH3:7])=[N:5][N:4]=[C:3]1[SH:8].[OH-].[Li+].[I-].[Na+].[C:13]([C:17]1[N:22]=[C:21]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][Cl:32])[CH2:25][CH2:24]2)[CH:20]=[C:19]([CH:33]2[CH2:35][CH2:34]2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14]>CN(C)C=O>[ClH:32].[C:13]([C:17]1[N:22]=[C:21]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][S:8][C:3]3[N:2]([CH3:1])[C:6]([CH3:7])=[N:5][N:4]=3)[CH2:25][CH2:24]2)[CH:20]=[C:19]([CH:33]2[CH2:34][CH2:35]2)[N:18]=1)([CH3:14])([CH3:15])[CH3:16]

참가 물질

6

반응물 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 690261252-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidineHCID 178434152HCID 178434152, 화합물

생성물 1

HCID 690806332-tert-Butyl-4-{4-[3-(4-methyl-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclopropyl-pyrimidine hydrochloride

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
80 °C

실험 절차

0.23 g of 4-Methyl-5-methyl-4H-[1,2,4]triazole-3-thiol (1.78 mmol), 0.04 g lithium hydroxide (1.78 mmol) and 0.13 g sodium iodide (0.89 mmol) were dissolved in 20 ml of dimethylformamide. Within 2 h, 0.6 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine (1.78 mmol), dissolved in 5 ml dimethylformamide, were added at 70° C. The mixture was stirred for 1 h at 80° C. After cooling to room temperature, the solvent was evaporated and the oily residue partitioned between 30 ml of ethyl acetate and 15 ml of water plus 15 ml of a saturated solution of sodium chloride in water. The aqueous layer was reextracted twice with 20 ml of ethyl acetate each, the organic phases combined, dried over magnesium sulfate, filtered, and the solvent was evaporated. The residue was purified by column chromatography on silica gel using ethyl acetate, ethyl acetate-methanol 9:1, and ethyl acetate-methanol 1:1. Fractions containing the product were combined. After evaporation of the solvent, the residue was re-dissolved in diisopropylethyl ether and a 1 N solution of HCl in diethylether was added. The precipitated hydrochloride salt was collected by filtration. Yield: 343 mg.

후처리

  1. additionwere added at 70° C
  2. temperatureAfter cooling to room temperature
  3. customthe solvent was evaporated
  4. customthe oily residue partitioned between 30 ml of ethyl acetate and 15 ml of water plus 15 ml of a saturated solution of sodium chloride in water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by column chromatography on silica gel
  9. additionFractions containing the product
  10. customAfter evaporation of the solvent
  11. dissolutionthe residue was re-dissolved in diisopropylethyl ether
  12. additiona 1 N solution of HCl in diethylether was added
  13. filtrationThe precipitated hydrochloride salt was collected by filtration

출처 및 근거

ORD 기록
ord-c525d7240aad4a18851121093fd34ebe
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202868B2

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