Acetylpyrazine → 4-[1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-1,3-benzodiazol-6-yl]-2-(pyrazin-2-yl)but-3-yn-2-ol

HRID 1398701Notes

Reaction equation

HRID 1398701 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([CH3:11])[N:8]([C:12]3[N:17]=[CH:16][N:15]=[C:14]([NH2:18])[N:13]=3)[C:7]=2[CH:19]=1)#[CH:2].[Li+].CC([N-]C(C)C)C.[N:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1[C:34](=[O:36])[CH3:35]>C1COCC1>[NH2:18][C:14]1[N:15]=[CH:16][N:17]=[C:12]([N:8]2[C:7]3[CH:19]=[C:3]([C:1]#[C:2][C:34]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][N:28]=4)([OH:36])[CH3:35])[CH:4]=[CH:5][C:6]=3[N:10]=[C:9]2[CH3:11])[N:13]=1

Participants

5

Reactant 3

HCID 30914AcetylpyrazineHCID 2724682Lithium diisopropylamideHCID 866696174-(6-Ethynyl-2-methyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine

Product 1

HCID 601651444-[1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-1,3-benzodiazol-6-yl]-2-(pyrazin-2-yl)but-3-yn-2-olYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 4-(6-ethynyl-2-methyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine (80 mg, 0.29 mmol) in THF (0.5 mL) at −78° C. under N2 (g) was added 2M LDA in THF (0.43 mL, 0.86 mmol). After 5 min 1-pyrazin-2-yl-ethanone (105 mg, 0.86 mmol) in THF (0.5 mL) was added. After 20 min, the mixture was allowed to warm to RT and was stirred for 1 hr. The reaction mixture was quenched by addition of sat aq NH4Cl (0.5 mL). The volatiles were removed by evaporation under reduced pressure. The mixture was diluted with EtOAc (10 ml) and washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by Biotage chromatography (100% DCM to 8% MeOH/DCM) gave the title compound (15 mg, 14% yield); 1H NMR (250 MHz, DMSO) delta 1.86 (3H, s), 2.89 (3H, s), 6.63 (1H, s), 7.32 (1H, dd, J=8.22, 1.52 Hz), 7.58 (1H, d, J=8.22 Hz), 7.96 (1H, s), 7.98 (1H, s), 8.39 (1H, d, J=1.22 Hz), 8.59-8.63 (1H, m), 8.63-8.67 (2 H, m), 9.02 (1H, d, J=1.37 Hz); LC-MS: m/z+373.4 (M+H)+.

Workup

  1. customThe reaction mixture was quenched by addition of sat aq NH4Cl (0.5 mL)
  2. customThe volatiles were removed by evaporation under reduced pressure
  3. additionThe mixture was diluted with EtOAc (10 ml)
  4. washwashed with water (2 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by Biotage chromatography (100% DCM to 8% MeOH/DCM)

Sources & evidence

ORD record
ord-c28edb652bff4046b55d6a4ef8152af3
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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