Tetrahydrofuran → 3-tert-butyl-1-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)urea

HRID 2276891노트

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HRID 2276891 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([N:23]3[CH2:28][CH2:27][C:26]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)([NH2:29])[CH2:25][CH2:24]3)=[O:22])[C:9]=2[CH3:36])=[CH:4][CH:3]=1.[C:37]([N:41]=[C:42]=[O:43])([CH3:40])([CH3:39])[CH3:38].C(N(CC)CC)C.O1CCCC1>ClCCl>[C:37]([NH:41][C:42](=[O:43])[NH:29][C:26]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:25][CH2:24][N:23]([C:21]([C:10]2[C:9]([CH3:36])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=2)=[O:22])[CH2:28][CH2:27]1)([CH3:40])([CH3:39])[CH3:38]

참가 물질

6

반응물 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 62412tert-Butyl isocyanate2회HCID 573428821-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-amine

생성물 1

HCID 573428853-tert-butyl-1-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)urea수율 45%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
40 °C

실험 절차

1-{[5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-amine (1 eq, 39.3 mg, 0.073 mmol), tert-butyl isocyanate (1.5 eq, 0.013 mL, 0.109 mmol), and triethylamine (3.0 eq, 0.03 mL, 0.218 mmol) was stirred in dichloromethane (5 mL) for 16 h. Next, tetrahydrofuran (5 mL) and an additional 0.02 mL of tert-butyl isocyanate were added and the reaction was stirred for 16 h Finally, the reaction was heated to 40° C. for 16 h. The reaction was concentrated in vacuo. The crude reaction material was then purified by silica gel column chromatography using 0-100% ethyl acetate/hexane to yield pure 3-tert-butyl-1-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)urea (21 mg, 45%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.15 (s, 9H) 1.93-2.17 (m, 4H) 2.20 (s, 3H) 2.42 (br. s., 1H) 3.13-3.35 (m, 1H) 3.58 (br. s., 1H) 4.25 (br. s., 1H) 4.44 (s, 1H) 4.52-4.69 (m, 1H) 5.13 (s, 1H) 7.03-7.10 (m, 2H) 7.13-7.37 (m, 7H) 7.38-7.46 (m, 3H).

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude reaction material
  3. customwas then purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-8eb94f3b08714815ab8fe2e25526a056
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133128B2

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