Dimethylformamide → HCID 68651269, compound

HRID 646678Notes

Reaction equation

HRID 646678 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5](Br)=[CH:6][N:7]=1.C1[CH2:11][CH:10]1[C:12]([NH2:14])=O.[C:15]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)([O:17][CH3:18])=[O:16].C(N(CC)CC)C.CN([CH:38]=[O:39])C>C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:23]2[CH:24]=[C:19]([CH:20]=[CH:21][CH:22]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:4][C:3]=1[C:38]([NH:14][CH:12]1[CH2:10][CH2:11]1)=[O:39]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 87530665HCID 87530665, compound

Product 1

HCID 68651269HCID 68651269, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-amino-6-bromopyrazine-2-cyclopropylcarboxamide (5.0 g, 19.4 mmole), [1,1′bis-(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (0.88 g, 1.9 mmol), 3-carbomethoxyphenylboronic acid (4.2 g, 23.3 mmol) in DMF (30 mL) was de-gassed with nitrogen. Triethylamine (5.4 mL, 38.9 mmol) was then added and the resulting mixture was heated at 85° for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL), filtered over silica gel, washed with saturated sodium bicarbonate solution (150 mL), dried over sodium sulfate, filtered, and concentrated. The oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield) to give methyl 3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate (a tan color solid, 4.5 g, 74% yield): 1H NMR (400 MHz, DMSO-d6): 8.67 (s, 1H), 8.50-8.49 (t, 1H), 8.07-8.03 (m, 2H), 7.57-7.54 (t, 1M), 3.98 (s, 3H), 2.91-2.88 (m, 1H), 0.94-0.85 (m, 2H), 0.72-0.62 (m, 2H); MS (EI) for C16H16N4O3: 428 (MH+).

Workup

  1. customwas de-gassed with nitrogen
  2. temperaturethe resulting mixture was heated at 85° for 2.5 hours
  3. filtrationfiltered over silica gel
  4. washwashed with saturated sodium bicarbonate solution (150 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield)

Sources & evidence

ORD record
ord-f1c7f8fbefa24d90b7a660d1dd3552c9
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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