2,3-Diaminopyridine → 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-imidazo[4,5-b]pyridine

HRID 751289ノート

反応式

HRID 751289 の反応式
[NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][N:3]=1.P(Cl)(Cl)(Cl)=O.[N:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[C:21]([C:28](O)=O)=[C:22]2[CH2:27][CH2:26][CH2:25][N:23]2[N:24]=1>Cl>[N:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[C:21]([C:28]2[NH:8][C:7]3[C:2]([N:1]=2)=[N:3][CH:4]=[CH:5][CH:6]=3)=[C:22]2[CH2:27][CH2:26][CH2:25][N:23]2[N:24]=1

参加物

5

反応物 3

HCID 99562,3-DiaminopyridineHCID 24813Phosphorus oxychlorideHCID 597100292-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylic Acid

生成物 1

HCID 100862642-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-imidazo[4,5-b]pyridine収率 48.2%

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid溶媒

実験手順

Add 2,3-diaminopyridine (Fluka; 120 mg, 1.09 mmol) and phosphorous oxychloride (4.4 mL) to 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylic acid (Preparation 3; 251 mg, 1.09 mmol) and heat the reaction at 106° C. for 3 h. Cool the reaction to 0° C. and add 1N aqueous hydrochloric acid (10 mL) slowly and stir for 10 min. Neutralize the mixture with saturated aqueous sodium bicarbonate and extract with chloroform. Wash the combined organic layers with brine, dry with sodium sulfate, concentrate in vacuo, purify by flash column chromatography, and triturate with hexanes to provide the title compound (159 mg, 48%) as a tan solid. Mp 170-172° C. MS ESI+ m/e 303 (M+1). 1H NMR (CDCl3) δ 8.80 (br, 1H), 8.34 (m, 2H), 7.88 (m, 2H), 7.36 (m, 1H), 7.11 (m, 1H), 4.29 (m, 2H), 3.54 (m, 2H), 2.71 (m, 2H). HPLC: 96.3%, Rt=13.59 min. TLC (SiO2): Rf0.3 (1:3 [80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]/dichloromethane).

後処理

  1. temperatureheat
  2. customthe reaction at 106° C. for 3 h
  3. temperatureCool
  4. customthe reaction to 0° C.
  5. extractionNeutralize the mixture with saturated aqueous sodium bicarbonate and extract with chloroform
  6. washWash the combined organic layers with brine
  7. dry with materialdry with sodium sulfate
  8. concentrationconcentrate in vacuo
  9. custompurify by flash column chromatography
  10. customtriturate with hexanes

出典と根拠

ORDレコード
ord-7a82f0b9b1d74043bae92bc4fc0fad1c
出典データセット
uspto-grants-2008_07
特許番号
US07405299B2

反応ノート

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