Lithium borohydride → 1-{3-Amino-2-[(2,2-difluoro-3-hydroxypropyl)amino]phenyl}-3-(2,4-dichlorophenyl)thiourea

HRID 1628521ノート

反応式

HRID 1628521 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9](=[S:19])[NH:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[C:3]=1[NH:20][CH2:21][C:22]([F:29])([F:28])[C:23](OCC)=[O:24].[BH4-].[Li+]>O1CCCC1>[NH2:1][C:2]1[C:3]([NH:20][CH2:21][C:22]([F:28])([F:29])[CH2:23][OH:24])=[C:4]([NH:8][C:9]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])=[S:19])[CH:5]=[CH:6][CH:7]=1

参加物

4

反応物 2

HCID 4148881Lithium borohydrideHCID 86632899Ethyl 3-[(2-amino-6-{[(2,4-dichlorophenyl)carbamothioyl]amino}phenyl)amino]-2,2-difluoropropanoate

生成物 1

HCID 866329001-{3-Amino-2-[(2,2-difluoro-3-hydroxypropyl)amino]phenyl}-3-(2,4-dichlorophenyl)thiourea収率 11.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of ethyl 3-[(2-amino-6-{[(2,4-dichlorophenyl)carbamothioyl]amino}phenyl)amino]-2,2-difluoropropanoate (694.5 mg, 1.50 mmol) in tetrahydrofuran (10 mL) was added lithium tetrahydroborate (65.3 mg, 3.00 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min. The reaction mixture was quenched with H2O. The mixture was extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-50% ethyl acetate/n-hexane gradient mixture to give a title compound (70.0 mg) and a mixture contained the title compound. The mixture was purified by preparative HPLC to give the title compound as the trifluoroacetic acid salt. The salt was neutralized with aqueous saturated sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the title compound as a colorless amorphous (273.3 mg). Total amount was 343.3 mg (0.815 mmol, 54%).

後処理

  1. customThe reaction mixture was quenched with H2O
  2. extractionThe mixture was extracted with ethyl acetate (×3)
  3. washThe combined organic layer was washed with brine (×1)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 0-50% ethyl acetate/n-hexane gradient mixture

出典と根拠

ORDレコード
ord-442e4a17f9694ea89170bb544bcb23dd
出典データセット
uspto-grants-2014_07
特許番号
US08785460B2

反応ノート

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