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 418802노트

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HRID 418802 반응식
[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

참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 576159461h-Indazole,4-bromo-1-(2,4-difluorophenyl)-6-methyl-2회HCID 59010010(2R)-2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol2회

생성물 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-Pentanol수율 20.7%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7589f114058147e493c67e984f537779
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093281B2

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