Hydrochloric Acid → HCID 71534518, compound

HRID 1473205Notes

Reaction equation

HRID 1473205 reaction equation
[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[NH:19][CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1.[Li+].[OH-].Cl>O1CCCC1>[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([S:38]([C:35]3[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=3)(=[O:40])=[O:39])[CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[C:7]([OH:9])=[O:8])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 95884-Fluorobenzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 89463134methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Product 1

HCID 71534518HCID 71534518, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

An ice cold solution of methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (20 mg, 0.043 mmol) in Tetrahydrofuran (THF) (0.5 mL) was treated with NaH (9.93 mg, 0.248 mmol) and allowed to stir at 0° C. for 10 minutes. The mixture was then treated with 4-fluorobenzenesulfonyl chloride (39.4 mg, 0.199 mmol) in one portion. The mixture was stirred for 10 minutes, quenched with water and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resultant was dissolved in Tetrahydrofuran (THF) (0.500 mL), treated with 2M LiOH (0.4 mL, 0.800 mmol) (2 M) and then stirred at ambient temperature overnight. The mixture was cooled to 0° C., treated with HCl (1M) until pH<2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford the title compound. 1H NMR (400 MHz, CHLOROFORM-d) ppm 8.16-8.29 (m, 2H) 7.81-7.92 (m, 1H) 7.51-7.58 (m, 1H) 7.45-7.51 (m, 2H) 7.28-7.35 (m, 1H) 7.17-7.25 (m, 2H) 6.09-6.18 (m, 1H) 5.21-5.32 (m, 1H) 3.54-3.65 (s, 3H) 0.99 (s, 9H); LCMS (m/z) ES+=547 (M+1).

Workup

  1. stirringThe mixture was stirred for 10 minutes
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe resultant was dissolved in Tetrahydrofuran (THF) (0.500 mL)
  9. stirringstirred at ambient temperature overnight
  10. temperatureThe mixture was cooled to 0° C.
  11. extractionextracted with ethyl acetate
  12. washThe combined extracts were washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-cf816e019665489eae605760c23d53fe
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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