Triethylamine → HCID 68651837, compound

HRID 646669Notes

Reaction equation

HRID 646669 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][CH2:12][CH2:13][OH:14])=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH3:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.[CH2:25](N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[CH3:25][C:6]1[N:7]=[C:2]([NH2:1])[C:3]([C:9]([NH:11][CH2:12][CH2:13][OH:14])=[O:10])=[N:4][C:5]=1[C:20]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:15])[CH:21]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27339503-Tolylboronic acidHCID 86607831HCID 86607831, compound

Product 1

HCID 68651837HCID 68651837, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

The intermediate 3-amino-N-(2-hydroxyethyl)-6-bromopyrazine-2-carboxamide (108 mg, 0.4 mmole), [1,1′bis-(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (19 mg, 0.04 mmol), 3-methylphenylboronic acid (67 mg, 0.5 mmol) in DMF (2 mL) was de-gassed with nitrogen. Triethylamine (0.12 mL, 0.8 mmol) was then added and the resulting mixture was heated at 85° C. for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), filtered over silica gel, washed with saturated sodium bicarbonate solution (10 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-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide as a solid: (95 mg, 84% yield): 1H NMR (400 MHz, DMSO-d6): 8.78 (s, 1H), 8.78-8.61 (b, 1H), 7.89 (s, 1H), 7.49-7.52 (t, 1H), 7.51-7.49 (d, 1H), 7.14-7.12 (d,1H), 3.50-3.35 (m, 2H), 2.89-70 (m, 2H), 2.51 (s, 3H): MS (EI) for C14H16N4O2: 273 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered over silica gel
  3. washwashed with saturated sodium bicarbonate solution (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. 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-d764ced9bb3b4d289d63ba332468dde9
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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