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Binap, (A+-)- → 1-(2-(6-(hydroxymethyl)pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one

HRID 716047
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HRID 716047 반응식
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]2=[N:6][CH:7]=1.[NH2:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:32][OH:33])=[N:30][CH:31]=1.CC([O-])(C)C.[Na+].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>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]>[OH:33][CH2:32][C:29]1[N:30]=[CH:31][C:26]([NH:25][C:2]2[N:3]=[C:4]3[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]3=[N:6][CH:7]=2)=[CH:27][CH:28]=1
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참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 20583240(5-Aminopyridin-2-YL)methanolHCID 23676156Sodium t-butoxideHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

생성물 1

HCID 710153681-(2-(6-(hydroxymethyl)pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one
수율 36.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
110 °C

실험 절차

To a 35 ml seal tube, 1-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one (0.25 g, 0.000606 mole) and (5-aminopyridin-2-yl)methanol (0.09 g, 0.00728 mole) was taken in toluene (3.0 ml). The reaction mixture was purged with argon for 15 min at RT and NaOtBu (0.11 g, 0.00121 mole) was added and the reaction mixture was further purged for 30 min with argon. BINAP (0.037 g, 0.000060 mole) and Pd2(dba)3 (0.027 g, 0.000030 mole) were added and the reaction mixture was heated to 110° C. for 3 hrs. After completion of the reaction, the reaction mixture was filtered through celite bed and washed with ethyl acetate. Filtrate was collected and concentrated to afford crude product which was purified using column purification by eluting with 40-50% ethyl acetate in hexanes to yield 0.1 g of 1-(2-(6-(hydroxymethyl)pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one.

후처리

  1. customTo a 35 ml seal tube
  2. customThe reaction mixture was purged with argon for 15 min at RT
  3. customthe reaction mixture was further purged for 30 min with argon
  4. customAfter completion of the reaction
  5. filtrationthe reaction mixture was filtered through celite bed
  6. washwashed with ethyl acetate
  7. customFiltrate was collected
  8. concentrationconcentrated
  9. customto afford crude product which
  10. customwas purified
  11. customcolumn purification
  12. washby eluting with 40-50% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-f68197c05a504519909fdcd813f7d587
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09187487B2

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