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Binap, (A+-)- → 1,1,1-Trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-2-({[1-(2-fluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-4-methyl-2-pentanol

HRID 418808
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인쇄 미리보기

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HRID 418808 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][CH:36]=[CH:35][C:34]=1[F:39].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:5][C:4]([F:7])([F:6])[C:3]([CH2:2][NH:1][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][CH:36]=[CH:35][C:34]=1[F:39])([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]
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참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 179365862-(Aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol2회HCID 23676156Sodium t-butoxideHCID 576159291h-Indazole,4-bromo-1-(2-fluorophenyl)-6-methyl-2회

생성물 1

HCID 118491111,1,1-Trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-2-({[1-(2-fluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-4-methyl-2-pentanol
수율 22.5%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
120 °C

실험 절차

To a mixture of 2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol (Intermediate 18, 49.5 mg, 0.16 mmol) and 4-bromo-1-(2-fluorophenyl)-6-methyl-1H-indazole (Intermediate 26, 45.8 mg, 0.15 mmol) in toluene (0.75 mL) were added tris(dibenzylideneacetone)dipalladium(0) (6.9 mg, 0.075 mmol), racemic-BINAP (9.3 mg, 0.015 mmol) and sodium tert-butoxide (18.5 mg, 0.192 mmol). The mixture was heated in a microwave at 120° C. for 30 min and then cooled and partitioned between water and dichloromethane. The organic layer was separated, dried and purified by silica gel chromatography using the Flashmaster II (20 g cartridge) eluting with a 0:100 cyclohexane:ethyl acetate gradient over 60 minutes to give crude product (43.6 mg) which was purified further by mass-directed autopreparation to give the title compound (18 mg).

후처리

  1. temperaturecooled
  2. custompartitioned between water and dichloromethane
  3. customThe organic layer was separated
  4. customdried
  5. custompurified by silica gel chromatography
  6. washeluting with a 0:100 cyclohexane
  7. customethyl acetate gradient over 60 minutes to give crude product (43.6 mg) which
  8. customwas purified further by mass-directed autopreparation

출처 및 근거

ORD 기록
ord-857f13ae6f1442dea8067c6494c93a74
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093281B2

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