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

HRID 369354Notes

Reaction equation

HRID 369354 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.CON(C)[C:16]([C:18]1[CH:26]=[C:25]2[C:21]([C:22]([CH:28]([C:42]3[CH:50]=[CH:49][C:45]4[O:46][CH2:47][O:48][C:44]=4[CH:43]=3)[C:29]([NH:31][S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:34])=[O:33])=[O:30])=[CH:23][N:24]2[CH3:27])=[CH:20][CH:19]=1)=[O:17]>O1CCCC1>[O:46]1[C:45]2[CH:49]=[CH:50][C:42]([CH:28]([C:22]3[C:21]4[C:25](=[CH:26][C:18]([C:16]([C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=5)=[O:17])=[CH:19][CH:20]=4)[N:24]([CH3:27])[CH:23]=3)[C:29]([NH:31][S:32]([C:35]3[CH:36]=[CH:37][C:38]([CH3:41])=[CH:39][CH:40]=3)(=[O:34])=[O:33])=[O:30])=[CH:43][C:44]=2[O:48][CH2:47]1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 22467206N6-methoxy-N6,1-dimethyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1H-6-indolecarboxamideHCID 178418339Butyllithium

Product 1

HCID 224672383-{1-(1,3-Benzodioxol-5-yl)-2-[(4-methylphenyl)sulfonamido]-2-oxoethyl}-1-methyl-6-(2-pyridylcarbonyl)-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

n-Butyllithium (0.32 ml of 2.5M solution in hexane) was added to a stirred solution of 2-bromopyridine (0.08 ml, 0.8 mmol) in anhydrous tetrahydrofuran (5 ml) at -70° C. under a nitrogen atmosphere. After 30 minutes a solution of N6-methoxy-N6,1-dimethyl-3-{1-(1,3-benzodioxol-5yl)-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 4 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 of a mixture of 90% hexane and 10% ethyl acetate, through to 100% ethyl acetate, to give the title compound (42 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 of a mixture of 90% hexane and 10% ethyl acetate

Sources & evidence

ORD record
ord-342070f8b0c14fb6b991ca9bcd792a93
Source dataset
uspto-grants-2000_10
Patent number
US06136843

Reaction notes

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