Water → N-(2-hydroxy-2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine

HRID 1798862Notes

Reaction equation

HRID 1798862 reaction equation
[NH2:1][CH2:2][C:3]([CH3:6])([OH:5])[CH3:4].Cl[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][N:16]=2)[N:11]=[CH:10][C:9]=1[N+:18]([O-:20])=[O:19].O>ClCCl>[CH3:4][C:3]([OH:5])([CH3:6])[CH2:2][NH:1][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][N:16]=2)[N:11]=[CH:10][C:9]=1[N+:18]([O-:20])=[O:19]

Participants

5

Reactant 3

HCID 962WaterHCID 951022-Propanol, 1-amino-2-methyl-HCID 131227874-Chloro-3-nitro-1,5-naphthyridine

Product 1

HCID 22172695N-(2-hydroxy-2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amineYield 10.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Under a nitrogen atmosphere, 1-amino-2-methylpropan-2-ol (25.5 g, 0.28 mol) was added over a period of 30 minutes to a solution of 4-chloro-3-nitro[1,5]naphthyridine (54.5 g, 0.26 mol) in dichloromethane (1 L). A water bath was used to control the exotherm and maintain the temperature of the reaction at or below 27° C. The reaction mixture was stirred at ambient temperature overnight. The resulting precipitate (crop 1) was isolated by filtration. The filtrate was concentrated under reduced pressure to provide crop 2. The two crops were slurried separately with de-ionized water for 2 hours and then isolated by filtration. Crop 1: 40.53 g of 2-methyl-2-[(3-nitro[1,5]naphthyridin-4-yl)amino]propan-2-ol as a yellow solid. Crop 2: tan solid. Crop 2 was dissolved in dichloromethane and loaded onto an alumina column. The column was eluted first with 1% methanol in dichloromethane and then with acetone. The combined eluents were concentrated under reduced pressure. The residue was recrystallized from ethanol (10 mL/g) to provide 6.95 g of 2-methyl-1-[(3-nitro[1,5]naphthyridin-4-yl)amino]propan-2-ol.

Workup

  1. customA water bath was used
  2. temperaturemaintain
  3. customthe temperature of the reaction at or below 27° C
  4. customThe resulting precipitate (crop 1) was isolated by filtration
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto provide crop 2
  7. customisolated by filtration
  8. washThe column was eluted first with 1% methanol in dichloromethane
  9. concentrationThe combined eluents were concentrated under reduced pressure
  10. customThe residue was recrystallized from ethanol (10 mL/g)

Sources & evidence

ORD record
ord-efc4fe5fe3cc487f9da534b82c11b0ad
Source dataset
uspto-grants-2013_01
Patent number
US08343993B2

Reaction notes

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