Dimethylformamide → HCID 10022054, compound

HRID 751319Notes

Reaction equation

HRID 751319 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:16]3[CH:25]=[C:24]4[C:19]([N:20]=[CH:21][C:22](=O)[NH:23]4)=[CH:18][CH:17]=3)=[C:10]3[CH2:15][CH2:14][CH2:13][N:11]3[N:12]=2)[CH:5]=[CH:4][CH:3]=1.C[N:28]([CH:30]=[O:31])C>O=P(Cl)(Cl)Cl.C(Cl)(Cl)Cl.C(O)(C)C.[C-]#N.[C-]#N.[Zn+2].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>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:16]3[CH:25]=[C:24]4[C:19]([N:20]=[CH:21][C:22]([C:30]([NH2:28])=[O:31])=[N:23]4)=[CH:18][CH:17]=3)=[C:10]3[CH2:15][CH2:14][CH2:13][N:11]3[N:12]=2)[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 11724985HCID 11724985, compound

Product 1

HCID 10022054HCID 10022054, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 24813Phosphorus oxychlorideSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

Reflux 7-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-quinoxalin-2-one (Example 55b; 20 mg, 0.055 mmol,) in POCl3 overnight. After removing POCl3, treat the residue with Zn(CN)2 (11.6 mg, 0.11 mmol) and Pd(PPh3)4 (3 mg, 0.003 mmol) in DMF (1 mL) at 100° C. for 20 min in microwave. Cool the solution to room temperature, dilute with chloroform/isopropyl alcohol and wash with brine. Dry the solution over sodium sulfate, filter, and evaporate the solvents to give a viscous mixture. Purify the crude product by column chromatography eluting with a gradient from dichloromethane to 10% methanol in dichloromethane to give the desired compound 12 mg (59%). MS (electrospray, m/z) 371.2 (M+1).

Workup

  1. customAfter removing POCl3
  2. washwash with brine
  3. dry with materialDry the solution over sodium sulfate
  4. filtrationfilter
  5. customevaporate the solvents
  6. customto give a viscous mixture
  7. customPurify the crude product by column chromatography
  8. washeluting with a gradient from dichloromethane to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-71860f4ea0c14fa787d70122af074dc3
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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