Binap, (A+-)- → HCID 73295442, compound

HRID 522975Notes

Reaction equation

HRID 522975 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][NH:8][C:5]2=[N:6][CH:7]=1.Cl.[NH2:19][C:20]1[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=1[C:22]([N:24]([CH3:26])[CH3:25])=[O:23].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.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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:19][C:20]3[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=3[C:22](=[O:23])[N:24]([CH3:25])[CH3:26])[N:3]=2)[NH:8][CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 20982453HCID 20982453, compoundHCID 23676156Sodium t-butoxideHCID 866779952-bromo-N-tert-butyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 73295442HCID 73295442, compoundYield 16%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-bromo-N-tert-butyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (80 mg, 269 μmol), 2-amino-N,N-dimethylbenzamide hydrochloride (81.0 mg, 404 μmol), BINAP (8.38 mg, 13.5 μmol), palladium (II) acetate (15.1 mg, 67.3 μmol) and sodium tert-butoxide (77.6 mg, 808 μmol, Eq: 3) 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 (15-45% dichloromethane/[10% dichloromethane/methanol/0.5% ammonium hydroxide]) gave N-tert-butyl-2(2(dimethylcarbamoyl)phenylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (16 mg, 42.1 μmol, 16%) as an off-white solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.25 (s, 1H), 8.77 (s, 1H), 8.06 (s, 1H), 7.96 (d, J=3.0, 1 H), 7.91 (d, J=7.9, 1 H), 7.78 (s, 1H), 7.38 (t, J=7.7, 1 H), 7.30 (d, J=7.5, 1 H), 7.11 (t, J=7.5, 1 H), 2.88 (s, 3H), 2.80 (s, 3H), 1.27 (s, 9H); MS (EI/CI) m/z: 381.2 [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 (15-45% dichloromethane/[10% dichloromethane/methanol/0.5% ammonium hydroxide])

Sources & evidence

ORD record
ord-c2d2ec06df7a4af5857541548bc591a6
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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