N,N-二异丙基乙胺 → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5,7-difluoro-1-benzofuran-2-carboxamide

HRID 15464

反应方程式

HRID 15464 反应方程式
[F:1][C:2]1[CH:3]=[C:4]([F:14])[C:5]2[O:9][C:8]([C:10]([OH:12])=O)=[CH:7][C:6]=2[CH:13]=1.Cl.Cl.[NH2:17][C@@H:18]1[CH:23]2[CH2:24][CH2:25][N:20]([CH2:21][CH2:22]2)[CH2:19]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:20]12[CH2:25][CH2:24][CH:23]([CH2:22][CH2:21]1)[C@@H:18]([NH:17][C:10]([C:8]1[O:9][C:5]3[C:4]([F:14])=[CH:3][C:2]([F:1])=[CH:13][C:6]=3[CH:7]=1)=[O:12])[CH2:19]2

参与物

6

反应物 4

HCID 81531N,N-二异丙基乙胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12494972R-3-氨基奎宁环二盐酸盐HCID 593414265,7-二氟苯并呋喃-2-羧酸

产物 1

HCID 59341435N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5,7-difluoro-1-benzofuran-2-carboxamide

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

55 mg (0.28 mmol) of 5,7-difluoro-1-benzofuran-2-carboxylic acid, 50 mg (0.25 mmol) of (R)-3-aminoquinuclidine dihydrochloride, 114.6 mg (0.3 mmol) of HATU, 117 mg (0.9 mmol) of N,N-diisopropylethylamine and 2.0 ml of DMF are reacted according to the general procedure (variant B). DMF is removed under reduced pressure and the crude product is dissolved in 1N aqueous sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over magnesium sulfate and the solvent is removed under reduced pressure using a rotary evaporator. The crude product is taken up in methanol and, together with acidic ion exchange resin (Dowex WX2-200), shaken for about 20 min. The loaded ion exchanger is washed three times with in each case 30 ml of methanol, then with water, again with methanol, with dichloromethane and finally again with methanol. The product is eluted with methanol/triethylamine 95:5. The solvent is removed under reduced pressure using a rotary evaporator. 40 mg (52% of theory) of the title compound are isolated.

后处理

  1. customDMF is removed under reduced pressure
  2. dissolutionthe crude product is dissolved in 1N aqueous sodium hydroxide solution
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. dry with materialThe combined organic phases are dried over magnesium sulfate
  5. customthe solvent is removed under reduced pressure
  6. customa rotary evaporator
  7. washThe loaded ion exchanger is washed three times with in each case 30 ml of methanol
  8. washThe product is eluted with methanol/triethylamine 95:5
  9. customThe solvent is removed under reduced pressure
  10. customa rotary evaporator

来源与证据

ORD记录
ord-bb2b1acbb9aa4d18911994645d145dcd
来源数据集
uspto-grants-2010_06
专利号
US07732477B2

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