Potassium Carbonate → N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide

HRID 600523Notes

Reaction equation

HRID 600523 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@H:19]2[CH2:23][CH2:22][N:21]([CH3:24])[C:20]2=[O:25])[CH:17]=1)[C:5]([NH:7][C:8]1[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].[N:26]1([C:30]([C:32]2[N:33]=[CH:34][C:35](Cl)=[N:36][CH:37]=2)=[O:31])[CH2:29]C[CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:27][N:26]([CH3:29])[C:30]([C:32]1[CH:37]=[N:36][C:35]([O:1][C:2]2[CH:3]=[C:4]([C:5](=[O:6])[NH:7][C:8]3[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=3)[CH:15]=[C:16]([O:18][C@H:19]3[CH2:23][CH2:22][N:21]([CH3:24])[C:20]3=[O:25])[CH:17]=2)=[CH:34][N:33]=1)=[O:31]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 24953713N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamideYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (188 mg, 0.55 mmol), 5-(azetidin-1-ylcarbonyl)-2-chloropyrazine (CAS no. 915949-00-7) (712 mg, 3.6 mmol) and potassium carbonate (152 mg, 0.55 mmol) in acetonitrile (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated to dryness then diluted with ethyl acetate (30 mL), washed with water (2×10 mL) and brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane to afford the product (210 mg, 78%). 1H NMR δ (300 MHz, CDCL3) 2.15-2.31 (m, 1H), 2.52-2.68 (m, 1H), 2.56 (s, 3H), 2.95 (s, 3H), 3.17 (d, 6H), 3.35-3.59 (m, 2H), 4.95 (t, 1H), 7.15 (s, 1H), 7.37 (s, 1H), 7.56 (s, 1H), 8.14 (s, 1H), 8.39 (s, 1H), 8.52 (s, 2H), 9.54 (s, 1H); m/z 492 (M+H)+.

Workup

  1. customThe solution was evaporated to dryness
  2. additionthen diluted with ethyl acetate (30 mL)
  3. washwashed with water (2×10 mL) and brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-fe4a74f9c0c04a4aab81ddb31fc0dc2b
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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