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Trifluoroacetic acid → 4-(2-amino-5-bromo-3-nitropyridin-4-yl)-N-phenylpiperazine-1-carboxamide

HRID 416756
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HRID 416756 반응식
[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19]C(C)(C)C)=O)[CH2:13][CH2:12]2)[C:5]([Br:24])=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.[C:41]1([N:47]=C=O)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([NH:47][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[O:19])[CH2:15][CH2:16]2)[C:5]([Br:24])=[CH:4][N:3]=1
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참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 7672Phenyl isocyanateHCID 81531DiisopropylethylamineHCID 46867806tert-Butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate

생성물 1

HCID 468682174-(2-amino-5-bromo-3-nitropyridin-4-yl)-N-phenylpiperazine-1-carboxamide수율 84.6%

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

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온도
0 °C

실험 절차

A solution of tert-butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate (250 mg, 0.62 mmol) in CH2Cl2 (2.5 mL) at 0° C. was treated with TFA (2.5 mL) and stirred at 0° C. for 1.5 h. After this time, the solvents were evaporated in vacuo and the excess TFA removed by azeotroping with toluene (3×10 ml). The residue was suspended in CHCl3 (2.5 mL) and treated with DIPEA (5 eq, 3.11 mmol, 0.54 mL) and phenyl isocyanate (1.05 eq, 0.65 mmol, 0.07 mL). The reaction was warmed to room temperature and stirred for 12 h. The formed precipitate was filtered off and dried to give the product as a yellow solid (221 mg, 84% for two steps); 1H-NMR (500 MHz, DMSO-d6) 3.07 (br s, 4H, piperazine N(CH2)2), 3.58 (br s, 4H, piperazine N(CH2)2), 6.94 (tt, J=7.4, 1.1 Hz, 1H, phenyl H-4), 7.03 (br s, 2H, NH2), 7.24 (dd, J=8.5, 7.5 Hz, 2H, phenyl H-3 & H-5), 7.45 (dd, J=8.5, 1.1 Hz, 2H, phenyl H-2 & H-6), 8.21 (s, 1H, pyridine H-6), 8.59 (br s, 1H, NH);

후처리

  1. customAfter this time, the solvents were evaporated in vacuo
  2. customthe excess TFA removed
  3. customby azeotroping with toluene (3×10 ml)
  4. temperatureThe reaction was warmed to room temperature
  5. stirringstirred for 12 h
  6. filtrationThe formed precipitate was filtered off
  7. customdried

출처 및 근거

ORD 기록
ord-ff26065cbc9a42de9f4a3ee48294feca
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08088761B2

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