Binap, (A+-)- → (2R)-2-({[1-(2,4-Difluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-Pentanol

HRID 418802ノート

反応式

HRID 418802 の反応式
[NH2:1][CH2:2][C@:3]([OH:21])([CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10])[C:4]([F:7])([F:6])[F:5].Br[C:23]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]2[C:24]=1[CH:25]=[N:26][N:27]2[C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:40][C:34]1[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=1[N:27]1[C:28]2[C:24](=[C:23]([NH:1][CH2:2][C@:3]([OH:21])([CH2:8][C:9]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[O:19][CH3:20])([CH3:11])[CH3:10])[C:4]([F:7])([F:6])[F:5])[CH:31]=[C:30]([CH3:32])[CH:29]=2)[CH:25]=[N:26]1

参加物

7

反応物 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 576159461h-Indazole,4-bromo-1-(2,4-difluorophenyl)-6-methyl-2 回HCID 59010010(2R)-2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol2 回

生成物 1

HCID 57615927(2R)-2-({[1-(2,4-Difluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-Pentanol収率 20.7%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

A solution of (2R)-2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol (Intermediate 21, 20 mg, 0.065 mmol), 4-bromo-1-(2,4-difluorophenyl)-6-methyl-1H-indazole (Intermediate 13, 18.3 mg, 0.057 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.6 mg, 0.0028 mmol), racemic-BINAP (3.6 mg, 0.0056 mmol) and sodium tert-butoxide (7.7 mg, 0.081 mmol) in toluene (0.4 mL) was heated in a microwave at 120° C. for 15 min. The mixture was then cooled, partitioned between ethyl acetate (20 mL) and aqueous ammonium chloride (20 mL). The organic layer was separated, washed successively with aqueous sodium bicarbonate, water and brine, passed through a hydrophobic frit and evaporated. The residue was purified by mass-directed autopreparation to give the title compound (6.5 mg).

後処理

  1. temperatureThe mixture was then cooled
  2. custompartitioned between ethyl acetate (20 mL) and aqueous ammonium chloride (20 mL)
  3. customThe organic layer was separated
  4. washwashed successively with aqueous sodium bicarbonate, water and brine
  5. customevaporated
  6. customThe residue was purified by mass-directed autopreparation

出典と根拠

ORDレコード
ord-7589f114058147e493c67e984f537779
出典データセット
uspto-grants-2012_01
特許番号
US08093281B2

反応ノート

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