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Binap, (A+-)- → (2S)-4-(2,3-Dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-{[(6-methyl-1-phenyl-1H-indazol-4-yl)amino]methyl}-2-pentanol

HRID 418803
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인쇄 미리보기

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HRID 418803 반응식
[NH2:1][CH2:2][C@@:3]([OH:21])([CH2:8][C:9]([C:12]1[C:20]2[O:19][CH2:18][CH2:17][C:16]=2[CH:15]=[CH:14][CH:13]=1)([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][CH:34]=1.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]>[O:19]1[C:20]2[C:12]([C:9]([CH3:11])([CH3:10])[CH2:8][C@@:3]([CH2:2][NH:1][C:23]3[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]4[C:24]=3[CH:25]=[N:26][N:27]4[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)([OH:21])[C:4]([F:6])([F:7])[F:5])=[CH:13][CH:14]=[CH:15][C:16]=2[CH2:17][CH2:18]1
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참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 15605604(2S)-2-(Aminomethyl)-4-(2,3-dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-pentanol2회HCID 23676156Sodium t-butoxideHCID 576159611h-Indazole,4-bromo-6-methyl-1-phenyl-2회

생성물 1

HCID 57615959(2S)-4-(2,3-Dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-{[(6-methyl-1-phenyl-1H-indazol-4-yl)amino]methyl}-2-pentanol
수율 28.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
120 °C

실험 절차

To a mixture of (2S)-2-(aminomethyl)-4-(2,3-dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-pentanol (Intermediate 31, 87 mg, 0.3 mmol) and 4-bromo-6-methyl-1-phenyl-1H-indazole (Intermediate 33, 92 mg, 0.32 mmol) in toluene (3.5 mL) were added tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.04 mmol), racemic-BINAP (28 mg, 0.04 mmol) and sodium tert-butoxide (45 mg, 0.47 mmol). The mixture was heated in a microwave at 120° C. for 15 min and then cooled and partitioned between ethyl acetate (30 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL), passed through a hydrophobic frit and evaporated. The residue was purified by two sequential SPE cartridge purifications eluting with a gradient of ethyl acetate:petroleum:ether (1:6 to 1:4) to give the title compound as a yellow foam (43 mg).

후처리

  1. temperaturecooled
  2. custompartitioned between ethyl acetate (30 mL) and water (20 mL)
  3. customThe organic layer was separated
  4. washwashed with water (20 mL)
  5. customevaporated
  6. customThe residue was purified by two sequential SPE cartridge purifications
  7. washeluting with a gradient of ethyl acetate:petroleum:ether (1:6 to 1:4)

출처 및 근거

ORD 기록
ord-07cbd7371bc144a7a4bfbe3e58ce3d6d
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093281B2

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