Dimethylformamide → HCID 131735547, compound

HRID 522950Notes

Reaction equation

HRID 522950 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[CH3:26][N:27]1[CH:31]=[CH:30][C:29]([NH2:32])=[N:28]1.CC(C)([O-])C.[Na+].CN(C=O)C>O.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>[C: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:30]=[CH:31][N:27]([CH3:26])[N:28]=3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 1372541-Methyl-3-aminopyrazoleHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 131735547HCID 131735547, compoundYield 67.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (200 mg, 468 μmol), 1-methyl-1H-pyrazol-3-amine (68.2 mg, 702 μmol), BINAP (14.6 mg, 23.4 μmol), palladium (II) acetate (26.3 mg, 117 μmol) and sodium tert-butoxide (112 mg, 1.17 mmol) was added DMF (1.01 mL) and toluene (503 μL) was heated in a microwave at 140° C. for 20 min. The reaction mixture was cooled then diluted with water and extracted into ethyl acetate. The organic layers were combined and washed with brine and then dried over magnesium sulfate. Purification by chromatography (silica, 20-100% ethyl acetate in hexanes) gave N-tert-butyl-2-(1-methyl-1H-pyrazol-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (140 mg, 316 μmol, 67%) as a yellow solid. MS (EI/CI) m/z: 444.3.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted into ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. customPurification by chromatography (silica, 20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3b8b995b8a384ae9b953732856bd3525
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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