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 751289노트

반응식

HRID 751289 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 313Hydrochloric Acid용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7a82f0b9b1d74043bae92bc4fc0fad1c
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07405299B2

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