Water → HCID 178513493, compound

HRID 64328Notes

Reaction equation

HRID 64328 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:25]([C:26]([NH2:28])=[O:27])=[C:17]3[NH:18][C:19]4[CH:20]=[N:21][CH:22]=[CH:23][C:24]=4[N:16]3[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[BH4-].[Na+].O>C1COCC1.C(Cl)Cl>[CH2:29]([N:21]1[CH2:22][CH2:23][C:24]2[N:16]3[N:15]=[C:14]([C:11]4[CH:10]=[CH:9][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:13][CH:12]=4)[C:25]([C:26]([NH2:28])=[O:27])=[C:17]3[NH:18][C:19]=2[CH2:20]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 4311764Sodium borohydrideHCID 178513490HCID 178513490, compound

Product 1

HCID 178513493HCID 178513493, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of 2-(4-phenoxyphenyl)-4H-pyrazolo[1′,5′:1,2]imidazo[4,5-c]pyridine-3-carbox-amide (2.46 g, 0.0067 mol) in 150 mL of THF was added benzyl bromide (1.14 g, 0.0067 mol) dropwise, then the mixture was stirred at 65° C. overnight. After cooling down to RT, the mixture was concentrated, the residue was suspended in 150 mL of MeOH, NaBH4 (10 g, 0.26 mol) was added portionwise. The mixture was stirred at RT overnight. To the reaction was added 200 mL of water followed by 200 mL of DCM. The aqueous phase was further extracted with 100 mL of DCM. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to get the crude product which was chromatographed on 10 g of silica gel using DCM/MeOH (200/1 to 80/1) as eluant to afford 0.786 g (26%) of 6-benzyl-2-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[1′,5′:1,2]imidazo[4,5-c]pyridine-3-carboxamide as a tan foam. MS (ESI) m/e [M+1]+ 463.9.

Workup

  1. temperatureAfter cooling down to RT
  2. concentrationthe mixture was concentrated
  3. stirringThe mixture was stirred at RT overnight
  4. extractionThe aqueous phase was further extracted with 100 mL of DCM
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto get the crude product which
  9. customwas chromatographed on 10 g of silica gel

Sources & evidence

ORD record
ord-2d3cdd75abf346b9adfdb54ecc44134d
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

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