1-(4-Bromophenyl)-4-methylpiperazine → [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1889762노트

반응식

HRID 1889762 반응식
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH2:20])[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Br[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH:20][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]5)=[CH:26][CH:27]=4)[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]

참가 물질

4

반응물 3

HCID 118176751-(4-Bromophenyl)-4-methylpiperazineHCID 249469872,2'-Bis(dicyclohexylphosphino)-1,1'-biphenylHCID 575023768-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

생성물 1

HCID 49838268[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

실험 절차

To a solution of 1-(4-bromo-phenyl)-piperazine (1.47 g, 6.10 mmol) and acetic acid (0.42 mL, 7.4 mmol) in methanol (25 mL) was added 37% formaldehyde in water/methanol (56.7:37:6.3, water:formaldehyde:methanol, 5.6 mL, 180 mmol). The mixture was stirred at room temperature for 18 hours. The suspension was cooled to 5° C. in an ice/water bath and Sodium cyanoborohydride (4.98 g, 79.2 mmol) was added in small portions. The mixture was stirred and warmed to room temperature for 18 hours. The mixture was slowly poured into saturated aqueous ammonium chloride (200 mL) and stirred for 1 hour. The mixture was extracted with dichloromethane (3×75 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an oily solid. The material was placed under high vacuum for 18 hours to yield a white solid (1.54 g). 1-(4-Bromo-phenyl)-4-methyl-piperazine was isolated as a white solid (1.54 g, 99%) and was used without further purification. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.36-7.31 (m, 2H), 6.82-6.76 (m, 2H), 3.20-3.15 (m, 4H), 2.60-2.55 (m, 4H), 2.36 (s, 3H). MS=255, 257 (MH)+. 32b) [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (75.0 mg, 0.260 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (73.0 mg, 0.286 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (29.0 mg, 0.0530 mmol) as the ligand in a manner analogous to Step 2d. The reaction product was isolated as pale yellow solid (0.022 g, 18%). MP=242-244° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.47 (dd, J=6.7, 1.1 Hz, 1H), 8.25-8.20 (m, 2H), 8.10-8.06 (m, 2H), 7.63 (dd, J=7.4, 1.1 Hz, 1H), 7.51-7.46 (m, 2H), 7.01-6.95 (m, 2H), 6.67 (s, 1H), 3.20-3.15 (m, 4H), 3.10 (s, 3H), 2.62-2.58 (m, 4H), 2.36 (s, 3H). MS=463 (MH)+.

후처리

  1. customwas used without further purification

출처 및 근거

ORD 기록
ord-99600591bf004178beca6dccab327503
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501936B2

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