Potassium Carbonate → 4-(2,6-Dinitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 33594

반응식

HRID 33594 반응식
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=2[N+:11]([O-:13])=[O:12])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 118141-Chloro-2,6-dinitrobenzeneHCID 143452tert-Butyl piperazine-1-carboxylate

생성물 1

HCID 865848194-(2,6-Dinitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester수율 85%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred solution of 1.01 g (5.0 mmol) of 1-chloro-2,6-dinitrobenzene and 0.93 g (5.0 mmol) of 1-tert-butyloxycarbonylpiperazine in acetonitrile (5 mL) was added 1.38 g (10 mmol) of K2CO3. The mixture was heated to reflux for 48 h. The solvent was removed under reduced pressure. The crude product was partitioned between EtOAc (100 mL) and 20 mL of H2O. The organic layer was washed with H2O (2×20 mL), dried over Na2SO4 and concentrated. Column chromatography (silica, 10-20% EtOAc/hexanes) provided 1.31 g (85%) of 4-(2,6-dinitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester TLC (silica, 20% EtOAc/hexanes): Rf=0.35. 1H NMR (400 MHz, CDCl3): 7.75 (d, J=8.2 Hz, 2H), 7.25 (t, J=8.2 Hz, 1H), 3.30 (m, 4H), 2.95 (m, 2H), 1.44 (s, 9H). B. 1-[4-(2,6-Dinitro-phenyl)-piperazin-1-yl]-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-2-ol. 4-(2,6-Dinitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (220 mg, 0.63 mmol) was dissolved in 5.0 mL of CH2Cl2 and treated with 3.0 mL of trifluoroacetic acid. The reaction mixture was stirred at 25° C. for 1 h before all volatiles were removed. The solid was treated with CH2Cl2 (20 mL) and aqueous KOH (4 N, 10 mL). The organic layer was separated, dried over Na2SO4, and concentrated. The crude oil (67 mg) was dissolved in absolute EtOH (1.2 mL) and treated with 141 mg (0.35 mmol, 1.3 eq) of 5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. The reaction mixture was refluxed at 85° C. for 3 h and then the solvent was removed. Column chromatography purification (silica, 10-20% acetone/CH2Cl2) provided 150 mg (85%) of 1-[4-(2,6-dinitro-phenyl)-piperazin-1-yl]-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-2-ol. TLC (silica, 10% acetone/CH2Cl2): Rf=0.3. MS (electrospray): exact mass calculated for C27H30F3N7O7S, 653.19; m/z found, 654.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.71 (d, J=8.2 Hz, 2H), 7.64 and 7.58 (AB pattern, J=8.4 Hz, 4H), 7.20 (t, J=8.2 Hz, 1H), 4.54 (s, 2H), 4.29-4.12 (m, 2H), 3.66 (t, J=5.3 Hz, 2H), 3.70-2.95 (m, 9H), 2.91 (s, 3H), 2.67-2.32 (m, 4H).

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 48 h
  3. customThe solvent was removed under reduced pressure
  4. customThe crude product was partitioned between EtOAc (100 mL) and 20 mL of H2O
  5. washThe organic layer was washed with H2O (2×20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-f0c8b03e655d4719bea7263876e58dfe
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07429591B2

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