Dimethylacetamide → HCID 178498763, compound

HRID 2403697Notes

Reaction equation

HRID 2403697 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=2)[NH:4][N:3]=1.[CH3:15][N:16](C)C(=O)C>CO.C(OCC)(=O)C.[Zn].[C-]#N.[Zn+2].[C-]#N>[C:15]([C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=2)[NH:4][N:3]=1)#[N:16]

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 178498761HCID 178498761, compound

Product 1

HCID 178498763HCID 178498763, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
120 °C

Procedure

Methyl 3-bromo-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1.28 g, 5.01 mmol) was combined with N,N-dimethylacetamide (34 mL). To this mixture was added zinc dust (195 mg, 2.90 mmol) and zinc cyanide (1.20 g, 10.2 mmol). Nitrogen was bubbled through the mixture for 30 minutes. Then 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (611 mg, 0.749 mmol) was added and the reaction vessel was sealed. The reaction was heated to 120° C. for 65 hours. The reaction was diluted with 20% methanol/ethyl acetate and filtered through Celite. The filtrate was diluted with water and transferred to a separatory funnel. The phases were separated, and the organics were washed again with water and brine. The organics were then dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-75% ethyl acetate/heptanes) gave the title compound (390 mg, 39%). +ESI (M+H) 203.1.

Workup

  1. customNitrogen was bubbled through the mixture for 30 minutes
  2. additionThen 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (611 mg, 0.749 mmol) was added
  3. customthe reaction vessel was sealed
  4. filtrationfiltered through Celite
  5. additionThe filtrate was diluted with water
  6. customtransferred to a separatory funnel
  7. customThe phases were separated
  8. washthe organics were washed again with water and brine
  9. dry with materialThe organics were then dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash column chromatography (0-75% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-7095cd3c28d0427e9093c2f6712630d6
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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