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 751289Notes

Reaction equation

HRID 751289 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7a82f0b9b1d74043bae92bc4fc0fad1c
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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