Dimethylformamide → HCID 131735546, compound

HRID 522946Notes

Reaction equation

HRID 522946 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.Br[C:10]1[N:11]=[C:12]2[C:18]([C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:17][N:16]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:13]2=[N:14][CH:15]=1.CC(C)([O-])C.[Na+].CN(C=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[C:22]([NH:21][C:19]([C:18]1[C:12]2[C:13](=[N:14][CH:15]=[C:10]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[N:11]=2)[N:16]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:17]=1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 153482-Amino-5-methylpyridineHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 131735546HCID 131735546, compoundYield 58.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 5-methylpyridin-2-amine (38.0 mg, 351 μmol), 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 234 μmol) (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (7.28 mg, 11.7 μmol), palladium(II) acetate (13.1 mg, 58.5 μmol) and sodium tert-butoxide (56.2 mg, 585 μmol) was added DMF (1 mL) and toluene (500 μL) and the mixture heated in a microwave at 140° C. for 20 min. The dark mixture generated was poured into water and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (magnesium sulfate), filtered and purified by chromatography (silica, 30-70% ethyl acetate in hexanes) to give N-tert-butyl-2-(5-methylpyridin-2-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (62 mg, 136 μmol, 58%) as an off white solid. MS (EI/CI) m/z: 455.3 [M+H].

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. custompurified by chromatography (silica, 30-70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a63438f75fb74e96a5c8877608677b3c
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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