Water → Tert-butyl 2-(3-cyano-5-methyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

HRID 1052112Notes

Reaction equation

HRID 1052112 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([CH3:11])[CH:9]=2)[N:4]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:3]=1.O.[CH3:21][N:22](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:21]([C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([CH3:11])[CH:9]=2)[N:4]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:3]=1)#[N:22]

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 68283706Tert-butyl 2-(3-iodo-5-methyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

Product 1

HCID 68283337Tert-butyl 2-(3-cyano-5-methyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A mixture of tert-butyl 2-(3-iodo-5-methyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate (1.00 g, 2.55 mmol), Zn(CN)2 (329 mg, 2.55 mmol), Pd(dppf)C2 (208 mg, 0.25 mmol), Pd2(dba)3 (233 mg, 0.25 mmol), water (2.7 mL) and DMF (20 mL) was subjected to microwave irradiation at 120° C. for 30 min under argon. The reaction mixture was filtered through a pad of Celite and the filtrate was diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Phase separator) and concentrated under vacuum. The residual oil was purified by flash chromatography on silica gel (EtOAc/c-hexane 1:2 then 1:1) to give the title compound. MS (LC/MS): 273.0 [M+H]+; tR (HPLC conditions d): 3.04 min.

Workup

  1. customirradiation at 120° C. for 30 min under argon
  2. filtrationThe reaction mixture was filtered through a pad of Celite
  3. additionthe filtrate was diluted with water and EtOAc
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. customdried (Phase separator)
  8. concentrationconcentrated under vacuum
  9. customThe residual oil was purified by flash chromatography on silica gel (EtOAc/c-hexane 1:2

Sources & evidence

ORD record
ord-f3ea9d3ffeab4a76917169886534ba40
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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