Dichloromethane → 7-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine

HRID 751305Notes

Reaction equation

HRID 751305 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[C:18](B(O)O)=[C:19]2[CH2:24][CH2:23][CH2:22][N:20]2[N:21]=1.C(=O)(O)[O-].[Na+].C(Cl)Cl>C1C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[C:18]([C:2]2[CH:7]=[CH:6][N:5]3[CH:8]=[CH:9][N:10]=[C:4]3[CH:3]=2)=[C:19]2[CH2:24][CH2:23][CH2:22][N:20]2[N:21]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 196959017-Chloroimidazo(1,2-a)pyridineHCID 59710031(2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

Product 1

HCID 117796147-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridineYield 15.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Combine 7-chloro-imidazo[1,2-a]pyridine (PCT Appl. WO 01/38326 A2; 134 mg, 0.88 mmol) with 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 369 mg, 0.97 mmol) in the presence of tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.03 mmol) and 2M aqueous sodium bicarbonate (1.0 mL) in benzene (2.1 mL) and ethanol (0.3 mL). Heat the mixture for 67 h at 100° C. Dilute the reaction with methylene chloride (10 mL) and water (10 mL). Separate the layers and extract the aqueous layer with methylene chloride (2×10 mL). Combine the organic layers and dry over sodium sulfate. Filter the solution and evaporate the solvent. Purify the crude product by flash chromatography using the appropriate ammonia in methanol/methylene chloride mixture to give the title compound as a tan solid (41 mg, 15%). MS m/e (302.0, M+1). 1H NMR (CDCl3) δ 8.57 (m, 1H), 7.96 (dd, J=1, 7 Hz, 1H), 7.6 (m, 5H), 7.19 (m, 1H), 6.69 (dd, J=1, 7 Hz, 1H), 4.27 (t, J=8 Hz, 2H), 3.08(t, J=7 Hz, 2H), 2.71 (q, J=7 Hz, 2H).

Workup

  1. additionDilute
  2. customSeparate the layers
  3. extractionextract the aqueous layer with methylene chloride (2×10 mL)
  4. dry with materialCombine the organic layers and dry over sodium sulfate
  5. filtrationFilter the solution
  6. customevaporate the solvent
  7. customPurify the crude product by flash chromatography

Sources & evidence

ORD record
ord-5853e9a1ce2d46f29bb60b296d6eebcb
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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