Pyridine → (R)-N-{2-Chloro-3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2120380ノート

反応式

HRID 2120380 の反応式
[Cl:1][C:2]1[C:8]([F:9])=[C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:22])[N:18]([CH3:21])[CH2:19][CH3:20])=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].N1C=CC=CC=1.[F:29][C:30]([F:42])([F:41])[C@@:31]([O:36][Si](C)(C)C)([CH3:35])[C:32](Cl)=[O:33].NC1C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[C:8]([F:9])=[C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:22])[N:18]([CH3:21])[CH2:19][CH3:20])=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:32](=[O:33])[C@:31]([OH:36])([CH3:35])[C:30]([F:42])([F:41])[F:29]

参加物

6

反応物 4

HCID 1049PyridineHCID 6115AnilineHCID 10586677(S)-3,3,3-trifluoro-2-trimethylsilyloxy-2-methylpropanoyl chlorideHCID 234394162-Chloro-3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]aniline

生成物 1

HCID 69824101(R)-N-{2-Chloro-3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide収率 47.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

2-Chloro3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]aniline (Method 83; 580 mg, 1.7 mmol) was dissolved in DCM (6 ml) and pyridine (0.28 ml) was added. (S)-3,3,3-Trifluoro-2-(trimethylsilyloxy)-2-methylpropanoyl chloride (prepared from (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (Method 25) as described in J. Med. Chem., 1999, 42, 2741-2746) (508 mg) was dissolved in DCM (1 ml) and added to the aniline. The solution was stirred for 4 hours and then washed with HCl (2 M) to remove excess pyridine. The organic layer was evaporated to dryness, dissolved in MeOH (17 ml) and HCl (2M, 1.7 ml) was added. The solution was left to stir overnight at room temp. The MeOH was removed and the residue was partitioned between water and EtOAc. The aqueous layer was extracted twice with EtOAc, the organic layers were combined, washed with water, brine and dried by pouring down a Chem Elut column and eluting with EtOAc. The resulting solution was evaporated to dryness and purified by chromatography on a Bond Elut column, eluting with 5-65% EtOAc/hexane to yield the title compound (390 mg) as a white solid. NMR: 1.0 (s, 3H), 1.6 (3, 3H), 2.8 (s, 3H), 3.2 (d, 2H), 7.2 (d, 2H), 7.3 (d, 2H), 7.6 (t, 1H), 7.9 (s, 1H), 9.9 (s, 1H); m/z 477.

後処理

  1. washwashed with HCl (2 M)
  2. customto remove excess pyridine
  3. customThe organic layer was evaporated to dryness
  4. dissolutiondissolved in MeOH (17 ml)
  5. additionHCl (2M, 1.7 ml) was added
  6. waitThe solution was left
  7. stirringto stir overnight at room temp
  8. customThe MeOH was removed
  9. customthe residue was partitioned between water and EtOAc
  10. extractionThe aqueous layer was extracted twice with EtOAc
  11. washwashed with water, brine
  12. customdried
  13. additionby pouring down a Chem Elut column
  14. washeluting with EtOAc
  15. customThe resulting solution was evaporated to dryness
  16. custompurified by chromatography on a Bond Elut column
  17. washeluting with 5-65% EtOAc/hexane

出典と根拠

ORDレコード
ord-b10c29d6e9de49a4be7a52860aec1489
出典データセット
uspto-grants-2004_02
特許番号
US06689909B1

反応ノート

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