Sodium Hydroxide → HCID 68674708, compound

HRID 1804730Notes

Reaction equation

HRID 1804730 reaction equation
[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][N:12]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:39])[CH2:22][CH2:21]3)C(=O)OC(C)(C)C)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1.[OH-].[Na+]>O.Cl>[OH2:1].[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][NH:12][CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:39])[CH2:22][CH2:21]3)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 57815262tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

Product 1

HCID 68674708HCID 68674708, compoundYield 182.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent3×

Conditions

Temperature
45 °C

Procedure

To a suspension of 25.0 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate in 50 mL of water, 18 mL of concentrated hydrochloric acid was added dropwise at 28 to 39° C. The reaction mixture was stirred for 3 hours and 30 minutes at 40 to 50° C., cooled to room temperature, added with 17 mL of a 20% sodium hydroxide aqueous solution and 25 mL of water and heated to 60° C. The mixture was adjusted to pH 3 with concentrated hydrochloric acid and 25 mL of water was added thereto. Insoluble matter was filtered out at 50° C. and the filter residue was washed using 25 mL of water. The filtrate and the wash liquid were combined and heated to 40° C., added with 13.5 mL of a 20% sodium hydroxide aqueous solution, 150 mL of 2-butanone and 25 mL of water, and refluxed with heating to dissolve the solid matter. The reaction mixture was cooled to 10° C. and the solid product obtained by filtration was washed with water to give 19.3 g of 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one monohydrate as a light yellow solid.

Workup

  1. additionwas added dropwise at 28 to 39° C
  2. temperaturecooled to room temperature
  3. temperatureheated to 60° C
  4. additionwas added
  5. filtrationInsoluble matter was filtered out at 50° C.
  6. washthe filter residue was washed
  7. temperatureheated to 40° C.
  8. additionadded with 13.5 mL of a 20% sodium hydroxide aqueous solution, 150 mL of 2-butanone and 25 mL of water
  9. temperaturerefluxed
  10. temperaturewith heating
  11. dissolutionto dissolve the solid matter
  12. temperatureThe reaction mixture was cooled to 10° C.
  13. customthe solid product obtained by filtration
  14. washwas washed with water

Sources & evidence

ORD record
ord-68b93a6867db4724a846f56f23951e7f
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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