Trifluoroacetic acid → 4-[5-amino-6-[5-[2-(2-aminoethoxy)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide

HRID 2204847

Reaktionsgleichung

Reaktionsgleichung von HRID 2204847
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:20]2[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][CH:21]=2)=[N:6][C:7]=1[C:8]1[O:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])=[N:11][N:12]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:38][CH2:39][NH:40]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:20]2[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][CH:21]=2)=[N:6][C:7]=1[C:8]1[O:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH2:38][CH2:39][NH2:40])=[N:11][N:12]=1

Komponenten

8

Edukt 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 1361172904-[5-amino-6-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide

Produkt 1

HCID 594719684-[5-amino-6-[5-[2-(2-aminoethoxy)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamideAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-[5-amino-6-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide (50 mg, 0.1228 mmol) in DMF (1.000 mL) was stirred at room temperature and potassium carbonate (25.46 mg, 0.1842 mmol) added. The resulting suspension was heated at 60-65° C. and tert-butyl N-(2-bromoethyl)carbamate (30.28 mg, 0.1351 mmol) was added slowly. After addition is complete the reaction mixture was heated overnight at 65° C. The reaction mixture was cooled to room temperature and water (2 mL) added slowly and the mixture stirred at room temperature for 20 min. A precipitate formed and was isolated by filtration and washed with water (3×5 mL). The solid was re-dissolved in CH2Cl2 and dried (MgSO4), filtered and evaporated to dryness. The solid was triturated with DCM/Ether, and filtered to leave a yellow solid. The yellow solid was in CH2Cl2 (1 mL) and TFA (150 μL, 1.947 mmol) added and the resulting solution stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and the residue taken up in a mixture of MeOH/CH2Cl2 (4 mL) and passed through a bicarbonate cartridge eluting with MeOH/DCM. The filtrate was evaporated to dryness and then triturated with acetonitrile to give the product as a yellow solid (36.7 mg, 69% yield) 1H NMR (400 MHz, DMSO) d 2.98 (s, 3H), 3.02 (s, 3H), 3.31 (t, 2H), 4.41 (t, 2H), 7.30 (t, 1H), 7.40 (d, 1H), 7.56 (d, 2H), 7.69-7.71 (m, 2H), 7.87 (s, 3H), 8.04 (dd, 1H), 8.16 (d, 2H) and 9.01 (s, 1H) ppm; MS (ES+) 446.28

Aufarbeitung

  1. temperatureThe resulting suspension was heated at 60-65° C.
  2. additionAfter addition
  3. temperaturewas heated overnight at 65° C
  4. temperatureThe reaction mixture was cooled to room temperature
  5. stirringthe mixture stirred at room temperature for 20 min
  6. customA precipitate formed
  7. customwas isolated by filtration
  8. washwashed with water (3×5 mL)
  9. dissolutionThe solid was re-dissolved in CH2Cl2
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customevaporated to dryness
  13. customThe solid was triturated with DCM/Ether
  14. filtrationfiltered
  15. customto leave a yellow solid
  16. stirringthe resulting solution stirred at room temperature for 2 h
  17. concentrationThe reaction mixture was concentrated in vacuo
  18. additionthe residue taken up in a mixture of MeOH/CH2Cl2 (4 mL)
  19. washeluting with MeOH/DCM
  20. customThe filtrate was evaporated to dryness
  21. customtriturated with acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-fc4d0545c4ba4f90a2623079f9ff940a
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365557B2

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