2-Fluoro-4-methylaniline → HCID 131735554, compound

HRID 522966Notes

Reaction equation

HRID 522966 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.[F:26][C:27]1[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:28]=1[NH2:29].CC(C)([O-])C.[Na+]>CN(C=O)C.C1(C)C=CC=CC=1.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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:29][C:28]3[CH:30]=[CH:31][C:32]([CH3:34])=[CH:33][C:27]=3[F:26])[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 3

HCID 679842-Fluoro-4-methylanilineHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 131735554HCID 131735554, compoundYield 53%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

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 (150 mg, 351 μmol), 2-fluoro-4-methylaniline (65.9 mg, 526 μmol), BINAP (10.9 mg, 17.5 μmol), palladium (II) acetate (19.7 mg, 87.7 μmol) and sodium tert-butoxide (84.3 mg, 877 μmol) in DMF (1 mL) and toluene (500 μL) was heated in a microwave at 140° C. for 20 min. The reaction mixture was diluted with water then extracted into ethyl acetate (3×). The combined organic extracts were washed with brine then dried over magnesium sulfate. Purification by chromatography (silica, 20-50% ethyl acetate/hexanes) gave N-tert-butyl-2-(2-fluoro-4-methylphenylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 184 μmol, 53%) as an off-white solid. MS (EI/CI) m/z: 470.1 [M−H].

Workup

  1. extractionthen extracted into ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialthen dried over magnesium sulfate
  4. customPurification by chromatography (silica, 20-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5dbf30ad772a4b26bcfaca9dd933253a
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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