2-Methylpyridine → 3-{1-(1,3-Benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1-methyl-6-[2-(2-pyridyl)acetyl]-1H-indole

HRID 1934634Notes

Reaction equation

HRID 1934634 reaction equation
O1CCCC1.C([N-]C(C)C)(C)C.[Li+].[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.CON(C)[C:24]([C:26]1[CH:34]=[C:33]2[C:29]([C:30]([CH:36]([C:50]3[CH:58]=[CH:57][C:53]4[O:54][CH2:55][O:56][C:52]=4[CH:51]=3)[C:37]([NH:39][S:40]([C:43]3[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][CH:44]=3)(=[O:42])=[O:41])=[O:38])=[CH:31][N:32]2[CH3:35])=[CH:28][CH:27]=1)=[O:25]>O1CCCC1>[O:54]1[C:53]2[CH:57]=[CH:58][C:50]([CH:36]([C:30]3[C:29]4[C:33](=[CH:34][C:26]([C:24](=[O:25])[CH2:14][C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=5)=[CH:27][CH:28]=4)[N:32]([CH3:35])[CH:31]=3)[C:37]([NH:39][S:40]([C:43]3[CH:44]=[CH:45][C:46]([CH3:49])=[CH:47][CH:48]=3)(=[O:42])=[O:41])=[O:38])=[CH:51][C:52]=2[O:56][CH2:55]1

Participants

5

Reactant 3

HCID 79752-MethylpyridineHCID 10997623Lithium diisopropylamide mono(tetrahydrofuran)HCID 22467206N6-methoxy-N6,1-dimethyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1H-6-indolecarboxamide2×

Product 1

HCID 224672333-{1-(1,3-Benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1-methyl-6-[2-(2-pyridyl)acetyl]-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Lithium diisopropylamide mono(tetrahydrofuran) (0.53 ml of 1.5M solution in cyclohexane) was added to a stirred solution of 2-methylpridine (0.08 ml, 0.8 mmol) in anhydrous tetrahydrofuran (3 ml) at −70° C. under a nitrogen atmosphere. After 20 minutes a solution of N6-methoxy -N6,1-dimethyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1H-6-indolecarboxamide (the compound of Example 103, 200 mg, 0.36 mmol) in anhydrous tetrahydrofuran (2 ml) was added to the mixture at −70° C. The mixture was stirred at −70° C. for an additional 2 hours before being warmed to 0° C., and then quenched with the addition of water (5 ml). The mixture was acidified with acetic acid, and extracted with ethyl acetate (100 ml). The organic phase was separated and washed with brine, dried (magnesium sulphate) and the solvent was removed in vacuo. The residue was flash chromatographed using a gradient elution or a mixture of 90% hexane and 10% ethyl acetate, through to 100% ethyl acetate, to give the title compound (95 mg).

Workup

  1. temperaturebefore being warmed to 0° C.
  2. customquenched with the addition of water (5 ml)
  3. extractionextracted with ethyl acetate (100 ml)
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried (magnesium sulphate)
  7. customthe solvent was removed in vacuo
  8. customchromatographed
  9. washa gradient elution
  10. additiona mixture of 90% hexane and 10% ethyl acetate

Sources & evidence

ORD record
ord-483c0bc55b3643269744853b3ab45e79
Source dataset
uspto-grants-2002_05
Patent number
US06384070B2

Reaction notes

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