Sodium Hydroxide → 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

HRID 1804729Notes

Reaction equation

HRID 1804729 reaction equation
O.[O:2]1[C:11]2[CH:10]=[C:9]([CH2:12][N:13]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=[CH:7][C:6]=2[O:5][CH2:4][CH2:3]1.O.Cl.[F:29][C:30]1[CH:39]=[C:38]2[C:33]([CH:34]=[CH:35][C:36](=[O:43])[N:37]2[CH2:40][CH:41]=O)=[N:32][CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>CN1CCCC1=O.O>[O:2]1[C:11]2[CH:10]=[C:9]([CH2:12][N:13]([CH:21]3[CH2:26][CH2:25][N:24]([CH2:41][CH2:40][N:37]4[C:38]5[C:33](=[N:32][CH:31]=[C:30]([F:29])[CH:39]=5)[CH:34]=[CH:35][C:36]4=[O:43])[CH2:23][CH2:22]3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=[CH:7][C:6]=2[O:5][CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 86646181(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde hydrochloride monohydrateHCID 86646182Tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate monohydrate

Product 1

HCID 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)carbamateYield 89.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a solution of 5.0 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate monohydrate in 40 mL of N-methyl-2-pyrrolidone, 3.5 g of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde hydrochloride monohydrate was added, and the mixture was stirred for 1 hour at room temperature. To the mixture, 4.3 g of sodium triacetoxyborohydride was added dividedly in 5 portions over the period of 80 minutes under ice cooling, and the mixture was stirred for 1 hour and 40 minutes under ice cooling. After heating to room temperature, the mixture was added with 20 mL of water and adjusted to pH 11.5 with an aqueous solution of 20% sodium hydroxide. To the mixture, 20 mL of N-methyl-2-pyrrolidone was added at 70 to 80° C., and the mixture was stirred for 2 hours and 30 minutes at the same temperature. The reaction mixture was cooled to room temperature and the solid product was obtained by filtration and washed with water to give 6.5 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 as a light brown solid.

Workup

  1. stirringthe mixture was stirred for 1 hour and 40 minutes under ice cooling
  2. temperatureAfter heating to room temperature
  3. stirringthe mixture was stirred for 2 hours and 30 minutes at the same temperature
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customthe solid product was obtained by filtration
  6. washwashed with water

Sources & evidence

ORD record
ord-2a96420c4889488391cd8081af700cf7
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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