Dimethylacetamide → Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1-methyl-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

HRID 2427807Notes

Reaction equation

HRID 2427807 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[C:36]3[C:31](=[C:32]([Cl:38])[CH:33]=[C:34]([Cl:37])[CH:35]=3)[NH:30][CH:29]=2)[CH:9]([C:13]2[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.[CH3:39]C(N(C)C)=O>CC([O-])(C)C.[K+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[C:36]3[C:31](=[C:32]([Cl:38])[CH:33]=[C:34]([Cl:37])[CH:35]=3)[N:30]([CH3:39])[CH:29]=2)[CH:9]([C:13]2[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 31374DimethylacetamideHCID 67262870Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

Product 1

HCID 67262866Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1-methyl-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

Reagents, catalysts & solvents 1

HCID 23665647Potassium tert-butoxideCatalyst

Procedure

A solution of KOtBu (1.0M THF, ca. 3 drops, 0.045 ml) was added to a dimethylacetamide solution (2 ml) of the intermediate from EXAMPLE 1, Step C (faster eluting enantiomer on ChiralPak AD 10% EtOH/Heptane, 4 mg, 0.007 mmol). Methyl iodide (three drops, excess) was then added dropwise. The progress of the reaction during the addition was monitored by MS-HPLC in order to minimize over alkylation. The reaction was quenched with aqueous 1N HCl. The mixture was extracted with EtOAc and the combined organics washed with water and brine. The solution was then dried over Na2SO4, filtered and concentrated to give the title compound which was used without further purification. LCMS1 4.40 min. (M+H)=585. The procedure was also carried out as described on the intermediate from Example 1, Step C (slower eluting enantiomer). LCMS1 4.39 min. (M+H)=585

Workup

  1. washfaster eluting enantiomer on ChiralPak AD 10% EtOH/Heptane, 4 mg, 0.007 mmol)
  2. additionMethyl iodide (three drops, excess) was then added dropwise
  3. customThe progress of the reaction
  4. additionduring the addition
  5. customThe reaction was quenched with aqueous 1N HCl
  6. extractionThe mixture was extracted with EtOAc
  7. washthe combined organics washed with water and brine
  8. dry with materialThe solution was then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6c7aa41e18524e03838be75649635e2d
Source dataset
uspto-grants-2011_06
Patent number
US07968589B2

Reaction notes

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