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

HRID 1036636Notes

Reaction equation

HRID 1036636 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH:11]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[C:13]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:12]1.[Si]([O:32][CH2:33][CH2:34][C@@H:35]1[CH2:37][N:36]1[S:38]([C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=1)(=[O:40])=[O:39])(C(C)(C)C)(C)C.I[CH3:49].Cl>CN(C=O)C>[F:47][C:44]1[CH:45]=[CH:46][C:41]([S:38]([N:36]([CH3:49])[C@H:35]([CH2:34][CH2:33][OH:32])[CH2:37][N:11]2[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[C:13]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:12]2)(=[O:40])=[O:39])=[CH:42][CH:43]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodide2×HCID 2724254Sodium bis(trimethylsilyl)amideHCID 25067325Methyl 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)acetateHCID 58399169(2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-phenyl)sulfonyl]aziridine

Product 1

HCID 86762092Methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-hydroxybutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a stirred solution of NaHMDS (177.22 g, 966 mmol) in DMF (600 ml) at −10° C. was added a solution of methyl 1H-pyrrolo[2,3-b]pyridin-3-ylacetate (197.98 g, 969 mmol) in DMF (1000 ml) over 15 min., and stirring continue at that temperature for 2 hours. To the anion was added a solution of (2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-phenyl)sulfonyl]aziridine (288 g, 801 mmol) in DMF (1000 ml) over 1 hour. The reaction mixture was stirred for 1 hour at −10° C. Iodomethane (125.0 ml, 1999 mmol) was added at −10° C. and the reaction was stirred for 1.5 hour. Another aliquot of iodomethane (20 mL) was then added and the reaction was stirred for 30 more minutes. 3N HCl (1800 ml, 5400 mmol) was added slowly at −10° C. and the reaction was stirred for an additional hour. The reaction was quenched by pouring into saturated sodium bicarbonate solution (4 L) and ethyl acetate (4 L). The pH was still acidic so additional solid sodium bicarbonate was added. The layers were separated and the organic layer washed with ½ brine (1×4 L) and (1×2 L).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour at −10° C
  2. stirringthe reaction was stirred for 1.5 hour
  3. stirringthe reaction was stirred for 30 more minutes
  4. stirringthe reaction was stirred for an additional hour
  5. customThe reaction was quenched
  6. additionby pouring into saturated sodium bicarbonate solution (4 L) and ethyl acetate (4 L)
  7. additionwas added
  8. customThe layers were separated
  9. washthe organic layer washed with ½ brine (1×4 L) and (1×2 L)

Sources & evidence

ORD record
ord-c1e53db69bce4ff386db4631a4d34f4f
Source dataset
uspto-grants-2013_10
Patent number
US08546422B2

Reaction notes

Loading…