Dimethyl Sulfoxide → Methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-oxobutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate

HRID 1036637Notes

Reaction equation

HRID 1036637 reaction equation
CS(C)=O.S(=O)(=O)=O.N1C=CC=CC=1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]([CH3:45])[C@H:26]([CH2:42][CH2:43][OH:44])[CH2:27][N:28]2[C:32]3=[N:33][CH:34]=[CH:35][CH:36]=[C:31]3[C:30]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C>ClCCl>[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]([CH3:45])[C@H:26]([CH2:42][CH:43]=[O:44])[CH2:27][N:28]2[C:32]3=[N:33][CH:34]=[CH:35][CH:36]=[C:31]3[C:30]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 168533Sulfur trioxide-pyridineHCID 86762092Methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-hydroxybutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate

Product 1

HCID 86762093Methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-oxobutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To DMSO (1 L, 1.41E+04 mmol) at room temperature was added pyridine sulfur trioxide (202.08 g, 1270 mmol) and the reaction mixture was stirred for 30 min at room temperature (solution A). In another flask, to a stirred solution of methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-hydroxybutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate (273 g, 589 mmol) and Hunig's base (0.425 L, 2433 mmol) in dichloromethane (4 L) at −10° C. was added solution A dropwise over 30 min. The reaction was stirred at −10° C. for 1 h. then quenched by adding ½ saturated brine (4 L); the aqueous layer was neutralized with solid sodium bicarbonate. The layers were then separated and the organic layer was washed with ½ saturated brine (4 L), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography with ethyl acetate to provide the title compound.

Workup

  1. customthen quenched
  2. additionby adding ½ saturated brine (4 L)
  3. customThe layers were then separated
  4. washthe organic layer was washed with ½ saturated brine (4 L)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash chromatography with ethyl acetate

Sources & evidence

ORD record
ord-7412807aa60847c3b55ee29bd92de4e2
Source dataset
uspto-grants-2013_10
Patent number
US08546422B2

Reaction notes

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