Dimethylformamide → HCID 178428484, compound

HRID 1952353Notes

Reaction equation

HRID 1952353 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[O:5][C:6]1[C:7](=[O:23])[N:8]([CH2:13][C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[NH:16][N:15]=2)[CH:9]=[CH:10][C:11]=1[CH3:12].[CH3:28][N:29](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:27][C:25]1[CH:26]=[C:2]([CH:3]=[C:4]([O:5][C:6]2[C:7](=[O:23])[N:8]([CH2:13][C:14]3[C:22]4[C:17](=[N:18][CH:19]=[CH:20][CH:21]=4)[NH:16][N:15]=3)[CH:9]=[CH:10][C:11]=2[CH3:12])[CH:24]=1)[C:28]#[N:29]

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 178428483HCID 178428483, compound

Product 1

HCID 178428484HCID 178428484, compound

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×

Conditions

Temperature
90 °C

Procedure

To a suspension of 3-(3-bromo-5-chlorophenoxy)-4-methyl-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)pyridin-2(1H)-one (11-6; 100 mg, 0.224 mmol) and zinc cyanide (29 mg, 0.247 mmol) in DMF (1 mL) was added palladium tetrakis triphenylphosphine (51.9 mg, 0.045 mmol) and the mixture was degassed and heated to 90° C. for 20 minutes. After this time, additional zinc cyanide (29 mg, 0.247 mmol) and palladium tetrakis triphenylphosphine (51.9 mg, 0.045 mmol) were added and the mixture heated to 90° C. for 20 hours. The reaction mixture was then filtered through Gelman Acrodisc and purified on Gilson LC using a Luna column (10μ, C18, 250×21.2 cm) eluting with 5-95% ACN/water with 0.1% TFA). Fractions containing desired compound were combine and the solvent concentrated in vacuo on a rotary evaporator. The residue was further purified using RediSep (4 g) and eluting with a 0-65% EtOAc/CH2Cl2 gradient. The desired fractions were combined and the solvent removed on the rotary evaporator to provide the title compound. 1H NMR (CDCl3): δ 11.48 (br s, 1H), 8.55 (d, 1H), 8.26 (d, 1H), 7.40 (d, 1H), 7.27 (dd, 1H), 7.14 (dd, 1H), 7.09 (dd, 1H), 6.96 (dd, 1H), 6.09 (dd, 1H), 5.48 (s, 2H) and 2.08 (s, 3H) ppm. LRMS (M+1)=392.

Workup

  1. customthe mixture was degassed
  2. temperaturethe mixture heated to 90° C. for 20 hours
  3. filtrationThe reaction mixture was then filtered through Gelman Acrodisc
  4. custompurified on Gilson LC
  5. washeluting with 5-95% ACN/water with 0.1% TFA)
  6. additionFractions containing desired compound
  7. concentrationthe solvent concentrated in vacuo on a rotary evaporator
  8. customThe residue was further purified
  9. washeluting with a 0-65% EtOAc/CH2Cl2 gradient
  10. customthe solvent removed on the rotary evaporator

Sources & evidence

ORD record
ord-a3396688834a41aeb5a7e7334fbf52be
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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