Reaction #165807

Reaction equation

TFA

potassium carbonate

4-[5-amino-6-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide

tert-butyl N-(2-bromoethyl)carbamate

→

product

Yield 69.0%

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

Yield 69.0%

Solvents

CH2Cl2

water

DMF

Conditions

Workup

1. 1
   TemperatureThe resulting suspension was heated at 60-65° C.
2. 2
   workup.ADDITIONAfter addition
3. 3
   Temperaturewas heated overnight at 65° C
4. 4
   TemperatureThe reaction mixture was cooled to room temperature
5. 5
   workup.STIRRINGthe mixture stirred at room temperature for 20 min
6. 6
   OtherA precipitate formed
7. 7
   Otherwas isolated by filtration
8. 8
   Washwashed with water (3×5 mL)
9. 9
   workup.DISSOLUTIONThe solid was re-dissolved in CH2Cl2
10. 10
    Dryingdried (MgSO4)
11. 11
    Filtrationfiltered
12. 12
    Otherevaporated to dryness
13. 13
    OtherThe solid was triturated with DCM/Ether
14. 14
    Filtrationfiltered
15. 15
    Otherto leave a yellow solid
16. 16
    workup.STIRRINGthe resulting solution stirred at room temperature for 2 h
17. 17
    ConcentrationThe reaction mixture was concentrated in vacuo
18. 18
    workup.ADDITIONthe residue taken up in a mixture of MeOH/ CH2Cl2 (4 mL)
19. 19
    Washeluting with MeOH/DCM
20. 20
    OtherThe filtrate was evaporated to dryness
21. 21
    Othertriturated with acetonitrile

Procedure

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

Source