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

HRID 416756
ノート
印刷プレビュー

反応式

HRID 416756 の反応式
[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

反応条件

温度
0 °C

実験手順

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);

後処理

  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

出典と根拠

ORDレコード
ord-ff26065cbc9a42de9f4a3ee48294feca
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08088761B2

反応ノート

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