Sodium Bicarbonate → 5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinone

HRID 2251042Notes

Reaction equation

HRID 2251042 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4]([CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])[C:5]([CH3:9])=[C:6]([Cl:8])[N:7]=1.[Cl:16][C:17]1[CH:18]=[C:19]([O:26][CH3:27])[CH:20]=[C:21]2[C:25]=1[NH:24][CH2:23][CH2:22]2.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C([O-])(O)=O.[Na+]>C1COCC1>[Cl:8][C:6]1[N:7]=[C:2]([N:24]2[C:25]3[C:21](=[CH:20][C:19]([O:26][CH3:27])=[CH:18][C:17]=3[Cl:16])[CH2:22][CH2:23]2)[C:3](=[O:15])[N:4]([CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])[C:5]=1[CH3:9]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 184527963,5-dichloro-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinoneHCID 184528147-Chloro-5-methoxyindoline

Product 1

HCID 102720535-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinoneYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Part C: A solution 3,5-dichloro-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinone from Part B (80 mg, 0.321 mmol) and 7-chloro-5-methoxyindoline (61.9 mg, 0.337 mmol) in THF (1.6 mL) was cooled to 0° C. and was treated with sodium hexamethyldisilazide (353 μL, 0.353 mmol, 1 M in THF). The reaction mixture was allowed to warm up to room temperature and was stirred overnight. The mixture was transferred to a separatory funnel containing saturated NaHCO3 and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (10% EtOAc in hexanes→40% EtOAc in hexanes) to provide the target compound (22 mg, 17% yield) as a brown oil: 1H NMR (CDCl3) δ 6.72 (s, 2 H), 4.27 (t, J=7.88 Hz, 2 H), 4.00-3.95 (m, 1 H), 3.77 (s, 3 H), 3.09 (t, J=7.8 Hz, 2H), 2.48-2.38 (m, 2 H), 2.42 (s, 3 H), 1.95-1.81 (m, 2 H), 0.87 (t, J=7.5 Hz, 6 H); HRMS (ESI) m/z 396.1259 [(M+H)+, calcd for C19H24N3O2Cl2 396.1246].

Workup

  1. customThe mixture was transferred to a separatory funnel
  2. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (10% EtOAc in hexanes→40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-448febfba65e41709c208eac9550e1de
Source dataset
uspto-grants-2008_01
Patent number
US07319100B2

Reaction notes

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