Methanol → ethyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-5-methoxypyrazine-2-carboxylate

HRID 1612365Notes

Reaction equation

HRID 1612365 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[Cl:30])[C:5]([C:19]([O:21][CH3:22])=[O:20])=[N:6][C:7]=1[NH:8][C@@H:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@@H:10]1[OH:18].[CH3:31][O-:32].[Na+].[CH3:34]O>CCOC(C)=O>[Cl:30][C:24]1[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=1[C:4]1[C:5]([C:19]([O:21][CH2:22][CH3:34])=[O:20])=[N:6][C:7]([NH:8][C@@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][C@@H:10]2[OH:18])=[C:2]([O:32][CH3:31])[N:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 58583474methyl 5-bromo-3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate

Product 1

HCID 68811012ethyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-5-methoxypyrazine-2-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 5-bromo-3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate (0.19 g, 0.37 mmol) in MeOH (3.7 mL) was added NaOMe (60 mg, 1.1 mmol). The mixture was heated at reflux for 3 hr. Cool to rt, and dilute with EtOAc. Wash with sat. aq. NaHCO3. Dry organic extract over MgSO4, filter and concentrate. Purify by biotage MPLC (90 g column, 25% ethyl acetate/hexanes) to afford 0.15 g (73%) of ethyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-5-methoxypyrazine-2-carboxylate as a solid: 1H NMR (CDCl3) δ 3.07-3.12, 3.25-3.31, 3.76, 4.04, 4.85-4.89, 5.68-5.76, 7.28-7.49; MS (ESI+) for C22H19Cl2N3O4 m/z 460 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 hr
  3. washWash with sat. aq. NaHCO3
  4. extractionDry organic extract over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by biotage MPLC (90 g column, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b6c79def37844d26a5fd65d5e03067db
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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