Pyridine → 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

HRID 1767088Notes

Reaction equation

HRID 1767088 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([OH:15])=O)=[CH:11][C:10]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[Cl:28][C:29]1[CH:30]=[C:31]([CH3:41])[C:32]2[NH:37]C(=O)[O:35][C:34](=O)[C:33]=2[CH:40]=1.N1C=CC=CC=1>ClCCl.C(N(CC)C=O)C.C(#N)C>[Cl:28][C:29]1[CH:30]=[C:31]([CH3:41])[C:32]2[N:37]=[C:13]([C:12]3[N:8]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=4)[N:9]=[C:10]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])[CH:11]=3)[O:15][C:34](=[O:35])[C:33]=2[CH:40]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 115502595-Chloro-3-methyl isatoic anhydrideHCID 211133851-(3-Chloropyridin-2-yl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 211133896-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

Reagents, catalysts & solvents 3

HCID 12051DiethylformamideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylic acid (i.e. product of Step C) (7.9 g, 24 mmol) stirred in dichloromethane (100 mL) was added N,N-diethylformamide (4 drops). Oxalyl chloride (4.45 g, 35 mmol) was added dropwise over a period of 45 minutes. The resulting solution was stirred at room temperature for 4 hours and then concentrated under vacuum. The isolated acid chloride was dissolved in dry acetonitrile (10 mL) and added to a suspension of 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (i.e. product of Step D) (4.9 g, 23 mmol) stirred in dry acetonitrile (14 mL). Pyridine (10 mL) was added, and the solution heated at reflux 6 hours. After cooling using an ice bath, a precipitate of white solid (9.15 g) was collected. The 1H NMR spectrum of the collected precipitate showed peaks consistent with the title compound and residual 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione starting material. A small portion of the collected precipitate was recrystallized from acetonitrile to yield the pure title product melting at 178–180° C.

Workup

  1. concentrationconcentrated under vacuum
  2. dissolutionThe isolated acid chloride was dissolved in dry acetonitrile (10 mL)
  3. temperaturethe solution heated
  4. temperatureat reflux 6 hours
  5. temperatureAfter cooling
  6. customa precipitate of white solid (9.15 g) was collected
  7. customA small portion of the collected precipitate was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-af2a7054287943db862d5f15d3baaa49
Source dataset
uspto-grants-2007_06
Patent number
US07232836B2

Reaction notes

Loading…