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Pyridine → 5-Bromo-3-nitro-4-(4-(phenylsulfonyl)piperazin-1-yl)pyridin-2-amine

HRID 416757
ノート
印刷プレビュー

反応式

HRID 416757 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(OC(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.N1C=CC=CC=1.[C:38]1([S:44](Cl)(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)Cl>[Br:24][C:5]1[C:6]([N:11]2[CH2:12][CH2:13][N:14]([S:44]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)(=[O:46])=[O:45])[CH2:15][CH2:16]2)=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([NH2:1])=[N:3][CH:4]=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 1049PyridineHCID 6422Trifluoroacetic acidHCID 7369Benzenesulfonyl chlorideHCID 46867806tert-Butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate

生成物 1

HCID 468683465-Bromo-3-nitro-4-(4-(phenylsulfonyl)piperazin-1-yl)pyridin-2-amine

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 (3 mL) and pyridine (3 mL) and treated with benzenesulfonyl chloride (1.1 eq, 0.68 mmol, 0.09 mL), warmed to room temperature and stirred for 12 h. The solvents were removed in vacuo and the residue partition between water (5 mL) and EtOAc (5 mL). The aqueous layer was extracted with EtOAc (2×5 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. Column chromatography (hexane-EtOAc, 1:1) gave the product (107 mg, 39% for two steps) as a yellow solid; 1H-NMR (500 MHz, DMSO-d6) 3.09 (br s, 8H, 2× piperazine N(CH2)2), 7.08 (br s, 2H, NH2), 7.67-7.70 (m, 2H, phenyl H-3 & H-5), 7.74-7.78 (m, 3H, phenyl H-2, H-4 & H-6), 8.16 (s, 1H, pyridine H-6);

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. temperaturewarmed to room temperature
  5. stirringstirred for 12 h
  6. customThe solvents were removed in vacuo
  7. customthe residue partition between water (5 mL) and EtOAc (5 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (2×5 mL)
  9. dry with materialthe combined organic extracts were dried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customColumn chromatography (hexane-EtOAc, 1:1) gave the product (107 mg, 39% for two steps) as a yellow solid

出典と根拠

ORDレコード
ord-9d9f8d6add3647629ca335e3517de56d
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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