Water → N-((1S,3R,4S)-3-ethyl-4-(2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropane-sulfonamide

HRID 1969877Notes

Reaction equation

HRID 1969877 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([N:8]2[C:17]3[C:12](=[CH:13][N:14]=[C:15]4[N:20](S(C5C=CC(C)=CC=5)(=O)=O)[CH:19]=[CH:18][C:16]4=3)[CH2:11][CH2:10][CH2:9]2)[CH2:6][C@@H:5]([NH:31][S:32]([CH:35]2[CH2:37][CH2:36]2)(=[O:34])=[O:33])[CH2:4]1)[CH3:2].[OH-].[Na+].O.CCOC(C)=O>O1CCOCC1>[CH2:1]([C@H:3]1[C@@H:7]([N:8]2[C:17]3[C:12](=[CH:13][N:14]=[C:15]4[NH:20][CH:19]=[CH:18][C:16]4=3)[CH2:11][CH2:10][CH2:9]2)[CH2:6][C@@H:5]([NH:31][S:32]([CH:35]2[CH2:36][CH2:37]2)(=[O:34])=[O:33])[CH2:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 58557285N-((1S,3R,4S)-3-ethyl-4-(7-tosyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropanesulfonamide

Product 1

HCID 53257644N-((1S,3R,4S)-3-ethyl-4-(2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropane-sulfonamideYield 72%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-((1S,3R,4S)-3-ethyl-4-(7-tosyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.041 g, 0.076 mmol) in 1,4-dioxane was added aqueous NaOH (5 N, 0.106 mL, 0.529 mmol). The reaction was heated to about 80° C. for about 16 h. The reaction mixture was cooled to ambient temperature and water (5 mL) and EtOAc (10 mL) were added. The layers were separated and the aqueous phase was extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to give N-((1S,3R,4S)-3-ethyl-4-(2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropane-sulfonamide (0.02 g, 72%) as a white solid: LC/MS (Table 1, Method a) Rt=1.48 min; MS m/z: 389 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (2×10 mL)
  4. dry with materialThe combined organics were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-c4e641120a354a6c9c1db0ef9b850acb
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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