Diisopropylethylamine → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-fluoro-7-bromo-1-benzofuran-2-carboxamide

HRID 335593

Reaction equation

HRID 335593 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Br: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]([Br:14])=[CH:3][C:2]([F:1])=[CH:13][C:6]=3[CH:7]=1)=[O:12])[CH2:19]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12494972(R)-(+)-3-Aminoquinuclidine DihydrochlorideHCID 179827017-Bromo-5-fluorobenzofuran-2-carboxylic acid

Product 1

HCID 59341405N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-fluoro-7-bromo-1-benzofuran-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

143 mg (0.55 mmol) of 5-fluoro-7-bromo-1-benzofuran-2-carboxylic acid, 100 mg (0.50 mmol) of (R)-3-aminoquinuclidine dihydrochloride, 229.14 mg (0.6 mmol) of HATU, 234 mg (1.81 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 and washed with saturated sodium chloride solution. 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. 181 mg (98% of theory) of the title compound are isolated.

Workup

  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. washwashed with saturated sodium chloride solution
  5. dry with materialThe combined organic phases are dried over magnesium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customa rotary evaporator
  8. washThe loaded ion exchanger is washed three times with in each case 30 ml of methanol
  9. washThe product is eluted with methanol/triethylamine 95:5
  10. customThe solvent is removed under reduced pressure
  11. customa rotary evaporator

Sources & evidence

ORD record
ord-64fc79a56820405084dd476c12f9feda
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Linked notes

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