Dimethylformamide → HCID 68512827, compound

HRID 549046Notes

Reaction equation

HRID 549046 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](OS(C(F)(F)F)(=O)=O)=[CH:8][CH:9]=2)[C:4]([C:19]2[N:27]([S:28]([C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)(=[O:30])=[O:29])[C:22]3=[N:23][CH:24]=[CH:25][CH:26]=[C:21]3[CH:20]=2)=[CH:3]1.CN(C)C=O.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C]=O.[C:74]([O:77][CH2:78]C)(=[O:76])C.CCCCC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C.CO>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:74]([O:77][CH3:78])=[O:76])=[CH:8][CH:9]=2)[C:4]([C:19]2[N:27]([S:28]([C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)(=[O:30])=[O:29])[C:22]3=[N:23][CH:24]=[CH:25][CH:26]=[C:21]3[CH:20]=2)=[CH:3]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 812191,3-Bis(diphenylphosphino)propaneHCID 22335286Ethyl acetate pentaneHCID 86590753HCID 86590753, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 68512827HCID 68512827, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

A solution of trifluoro-methanesulfonic acid 1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl ester [300 mg, Reference Example 18(a)] in a mixture of dry dimethylformamide (10 mL), methanol (6 mL) and triethylamine (2 mL) was treated with palladium acetate (24 mg) and 1,3 bis(diphenylphosphino)propane and the mixture stirred at ambient temperature for 30 minutes. Carbon-monoxide was introduced via a septum to the reaction vessel at a steady rate and the mixture heated at 90° C. until no starting material was present as indicated by TLC (ethyl acetate/pentane: 2/3). The mixture was then concentrated in vacuo and the residue partitioned between dichloromethane and water. The organic phase was washed with a saturated solution of lithium chloride, then dried over sodium sulfate and then evaporated. The residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3, v/v) to give the title compound (200 mg) as a colourless solid. MS: 460 (MH+). HPLC (METHOD A): RT=10.23 minutes.

Workup

  1. temperaturethe mixture heated at 90° C. until no starting material
  2. concentrationThe mixture was then concentrated in vacuo
  3. customthe residue partitioned between dichloromethane and water
  4. washThe organic phase was washed with a saturated solution of lithium chloride
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. additionThe residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3

Sources & evidence

ORD record
ord-92d14901528e462fa8294c820f409359
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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