Dimethylformamide → HCID 90041067, compound

HRID 522952Notes

Reaction equation

HRID 522952 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][CH:14]([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]2=[N:6][CH:7]=1.[CH3:25][C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1.CC(C)([O-])C.[Na+].CN(C=O)C>O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:32][C:29]3[CH:28]=[CH:27][C:26]([CH3:25])=[CH:31][N:30]=3)[N:3]=2)[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:9]=1)=[O:12])([CH3:16])[CH3:15]

Participants

10

Reactant 4

HCID 6228DimethylformamideHCID 153482-Amino-5-methylpyridineHCID 23676156Sodium t-butoxideHCID 585222792-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 90041067HCID 90041067, compoundYield 56.2%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 363 μmol), 5-methylpyridin-2-amine (58.9 mg, 544 μmol), BINAP (11.3 mg, 18.1 μmol), palladium (II) acetate (20.4 mg, 90.7 μmol) and sodium tert-butoxide (87.2 mg, 907 μmol) was added DMF (780 μL) and toluene (390 μL) was heated in a microwave at 140° C. for 20 min. The mixture was cooled then diluted with water and ethyl acetate. The mixture was extracted with ethyl acetate (3×) then the organic extracts were combined and washed with brine, dried over magnesium sulfate and purified by chromatography (silica, 30-70% ethyl acetate in hexanes) to give N-isopropyl-2-(5-methylpyridin-2-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (90 mg, 204 μmol, 56%) as an off-white solid. MS (EI/CI) m/z: 441.3 [M+H].

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. custompurified by chromatography (silica, 30-70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-63cc4ce6fb9144ec8307aef1bac37df0
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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