Water → 2-chloro-N-(2-chloro-6-methoxy-5-nitropyrimidin-4-yl)-5-(2-fluoro-6-methoxybenzyloxy)-4-methoxyaniline

HRID 1513086Notes

Reaction equation

HRID 1513086 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[C:4]([O:12][CH3:13])[N:3]=1.[Cl:14][C:15]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH2:25][C:26]2[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=2[F:34])=[CH:18][C:16]=1[NH2:17].C(N(CC)C(C)C)(C)C.O>C(#N)C>[Cl:14][C:15]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH2:25][C:26]2[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=2[F:34])=[CH:18][C:16]=1[NH:17][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[C:4]([O:12][CH3:13])[N:3]=[C:2]([Cl:1])[N:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 593096572-Chloro-5-(2-fluoro-6-methoxybenzyloxy)-4-methoxyanilineHCID 593099452,4-Dichloro-5-nitro-6-methoxypyrimidine

Product 1

HCID 867615882-chloro-N-(2-chloro-6-methoxy-5-nitropyrimidin-4-yl)-5-(2-fluoro-6-methoxybenzyloxy)-4-methoxyanilineYield 90.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2,4-dichloro-6-methoxy-5-nitropyrimidine (1.79 g) in acetonitrile (21 mL) were added 2-chloro-5-(2-fluoro-6-methoxybenzyloxy)-4-methoxyaniline (2.18 g) and N,N-diisopropylethylamine (1.28 mL), and the mixture was stirred at 40° C. for 3 days. To the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residual solids were suspended in a mixed solvent (n-hexane/ethyl acetate=3/1), and collected by filtration. The collected solids were dried under reduced pressure to give 2-chloro-N-(2-chloro-6-methoxy-5-nitropyrimidin-4-yl)-5-(2-fluoro-6-methoxybenzyloxy)-4-methoxyaniline (3.15 g). The title compound was prepared in a similar manner to that described in Example 397 using this material instead of 2-chloro-N-(2-chloro-6-methoxy-5-nitropyrimidin-4-yl)-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyaniline.

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. filtrationcollected by filtration
  6. customThe collected solids were dried under reduced pressure

Sources & evidence

ORD record
ord-f31d913764d240b5a8a723cf2306b80d
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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