Water → 5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone

HRID 2251000Notes

Reaction equation

HRID 2251000 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=1.Cl.[Cl:17][C:18]1[CH:19]=[C:20]([O:27][CH3:28])[CH:21]=[C:22]2[C:26]=1[NH:25][CH2:24][CH2:23]2.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O>O1CCCC1>[Cl:8][C:6]1[N:7]=[C:2]([N:25]2[C:26]3[C:22](=[CH:21][C:20]([O:27][CH3:28])=[CH:19][C:18]=3[Cl:17])[CH2:23][CH2:24]2)[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 184527983,5-dichloro-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinoneHCID 184528197-Chloro-5-methoxyindoline hydrochloride

Product 1

HCID 102008575-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinoneYield 20.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 3,5-dichloro-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone (1.0 g), prepared as described in Scheme 4, and 7-chloro-5-methoxyindoline hydrochloride (0.92 g), prepared as described in U.S. Pat. No. 6,245,769, stirring in anhydrous tetrahydrofuran (25 mL, 0° C.) was added sodium bis(trimethylsilyl)amide (1.0 M in THF, 11.9 mL, dropwise). The reaction mixture was allowed to come to ambient temperature and stirred 18 hours. Water was added, and the mixture was extracted with three portions of ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over MgSO4, and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford the title compound (329 mg). mp 131-133° C. 1H-NMR (CDCl3) δ: 0.93 (3H, t, J=7.3 Hz), 1.83 (2H, m), 3.09 (2H, t, J=7.6 Hz), 3.35 (3H, s), 3.56 (1H, dd), 3.67 (1H, dd), 3.78 (3H, s), 4.34 (2H, t, J=7.7 Hz), 4.94 (1H, m), 6.74 (2H, s), 6.99 (1H, s). MS (APCI+) m/z 398 (M+H)+.

Workup

  1. customprepared
  2. customto come to ambient temperature
  3. extractionthe mixture was extracted with three portions of ethyl acetate
  4. washThe combined ethyl acetate extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was chromatographed on silica gel

Sources & evidence

ORD record
ord-b8602ac3403e463ba2ba5befb6fef0c9
Source dataset
uspto-grants-2008_01
Patent number
US07319100B2

Reaction notes

Loading…