Dimethylformamide → HCID 58177313, compound

HRID 1916127Notes

Reaction equation

HRID 1916127 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[C:12]([NH:21][C@H:22]4[CH2:27][CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:23]4)=[N:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[N:15][CH:16]=3)[N:9]=2)[N:4]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:3]=1.[C:40]([Zn]C#N)#[N:41].CN(C)C=O>[Cl-].[Na+].O.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+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]>[CH3:20][S:17]([C:14]1[N:13]=[C:12]([NH:21][C@H:22]2[CH2:27][CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:23]2)[C:11]([C:8]2[N:9]=[C:10]3[C:2]([C:40]#[N:41])=[CH:3][N:4]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:5]3=[N:6][CH:7]=2)=[CH:16][N:15]=1)(=[O:19])=[O:18]

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 58177409HCID 58177409, compoundHCID 178514179HCID 178514179, compound

Product 1

HCID 58177313HCID 58177313, compoundYield 63.4%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of {5-[7-Iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-2-methanesulfonyl-pyrimidin-4-yl}-((S)-1-methanesulfonyl-piperidin-3-yl)-amine (65 mg, 0.091 mmol) and dicyanozinc (11 mg, 0.092 mmol) was combined with dimethylformamide (0.5 ml) (1% water) and the solution thoroughly degassed. To this was added 1,1′-bis(diphenylphosphino)ferrocene (dppf) (1.0 mg, 1.84 μmol) and Tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (4.2 mg, 4.6 μmol) and the mixture was heated to 120° C. for 1.5 hours. This was cooled, diluted with brine and water, extracted with ethyl acetate, dried and purified by flash chromatography (silica gel, 0% to 50% ethyl acetate/dichloromethane) to give 2-[2-methanesulfonyl-4-((S)-1-methanesulfonyl-piperidin-3-ylamino)-pyrimidin-5-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonitrile (35 mg, 63%). MS: (ES+): 607.

Workup

  1. customthe solution thoroughly degassed
  2. temperatureThis was cooled
  3. extractionextracted with ethyl acetate
  4. customdried
  5. custompurified by flash chromatography (silica gel, 0% to 50% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-60eecbe9bd9242a79d2b31b9cefdf778
Source dataset
uspto-grants-2013_12
Patent number
US08618103B2

Reaction notes

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