Dimethylformamide → N-tert-butyl-2-(1-methyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 522954Notes

Reaction equation

HRID 522954 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.Cl.[CH3:27][N:28]1[CH:32]=[C:31]([NH2:33])[CH:30]=[N:29]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:33][C:31]3[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=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 173542681-methyl-1H-pyrazol-4-amineHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 131735548N-tert-butyl-2-(1-methyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 57.3%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
140 °C

Procedure

To a mixture of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 351 mol), 1-methyl-1H-pyrazol-4-amine hydrochloride (70.3 mg, 526 mol), BINAP (10.9 mg, 17.5 mol), palladium (II) acetate (19.7 mg, 87.7 mol) and sodium tert-butoxide (84.3 mg, 877 mol) was added DMF (1 mL) and toluene (500 μL). After heating in a microwave at 140° C. for 20 min, the reaction mixture was cooled, diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, then dried over magnesium sulfate, and purified by chromatography (silica, 30-70% ethyl acetate in hexanes) to give N-tert-butyl-2-(1-methyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (89 mg, 201 mol, 57%) as a yellow solid. MS (EI/CI) m/z: 314.1 [M+H].

Workup

  1. temperaturethe reaction mixture was cooled
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed 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-7f4d5b9b82a74a428e243ccf9b3940d9
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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