Selectfluor → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropyrimidine-4-carboxylic acid methyl ester

HRID 495033Notes

Reaction equation

HRID 495033 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([NH2:11])[N:8]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19][CH3:20])[C:13]=2[F:21])[N:6]=1)=[O:4].[B-](F)(F)(F)[F:23].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([F:23])=[C:9]([NH2:11])[N:8]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19][CH3:20])[C:13]=2[F:21])[N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 594320836-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylic acid methyl ester

Product 1

HCID 669538936-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropyrimidine-4-carboxylic acid methyl esterYield 3.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

6-Amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)-pyrimidine-4-carboxylic acid methyl ester (778 mg, 2.5 mmol) and F-TEDA (974 mg, 2.75 mmol) were combined in acetonitrile and heated at reflux for 4 hours (reaction made little progress after 1 hour). The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated, purified by column chromatography, and then purified a second time by preparative HPLC to yield 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropyrimidine-4-carboxylic acid methyl ester (26 mg, 3.2% yield): mp 200-202° C.: 1H NMR (CDCl3): δ 7.62 (dd, 1H), 7.21 (dd, 1H), 5.40 (br s, 2H), 4.02 (s, 3H), 4.0 (d, 3H)

Workup

  1. temperatureheated
  2. temperatureat reflux for 4 hours
  3. custom(reaction made little progress after 1 hour)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by column chromatography
  7. custompurified a second time by preparative HPLC

Sources & evidence

ORD record
ord-20e26d7cd01d494a8cc953feabfdca0f
Source dataset
uspto-grants-2009_05
Patent number
US07538214B2

Reaction notes

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