Cesium carbonate → 9-(4-cyclopropylpiperazin-1-yl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

HRID 926114Notes

Reaction equation

HRID 926114 reaction equation
Br[C:2]1[CH:11]=[N:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:7](=[O:21])[N:6]3[N:22]=[CH:23][N:24]=[C:5]3[C:4]=2[CH:3]=1.[CH:25]1([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH2:27][CH2:26]1.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.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:25]1([N:28]2[CH2:33][CH2:32][N:31]([C:2]3[CH:11]=[N:10][C:9]4[N:8]([CH2:12][C:13]5[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=5)[C:7](=[O:21])[N:6]5[N:22]=[CH:23][N:24]=[C:5]5[C:4]=4[CH:3]=3)[CH2:30][CH2:29]2)[CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 47420041-CyclopropylpiperazineHCID 867053859-bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

Product 1

HCID 867053889-(4-cyclopropylpiperazin-1-yl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-oneYield 36.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

9-Bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 1, 63 mg, 0.16 mmol) and 1-cyclopropylpiperazine (103 mg, 0.82 mmol) were dissolved in toluene (2 mL) and nitrogen was bubbled through the mixture while BINAP (41 mg, 0.07 mmol), Cs2CO3 (159 mg, 0.49 mmol) and Pd(OAc)2 (7 mg, 0.03 mmol) were added. The mixture was heated at 100° C. for 16 h. The reaction mixture was concentrated under a stream of nitrogen and the residue was taken up in DMF and filtered. Purification (preparative HPLC, 10-70% ACN in water) afforded the title compound (25 mg, 27%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 0.84-1.00 (m, 2H), 1.38 (d, J=3.01 Hz, 2H), 2.01 (s, 2H), 2.35-2.51 (m, 1H), 3.50 (s, 4H), 3.61 (br s, 4H), 3.76 (s, 3H), 5.70 (s, 2H), 6.82 (d, J=8.53 Hz, 2H), 7.57 (d, J=8.41 Hz, 2H), 8.07 (d, J=2.89 Hz, 1H), 8.33 (s, 1H), 8.47 (d, J=2.89 Hz, 1H). [M+H]=432.2.

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated under a stream of nitrogen
  3. filtrationfiltered
  4. customPurification (preparative HPLC, 10-70% ACN in water)

Sources & evidence

ORD record
ord-83c8a21b0d114c889a9e44d629030d32
Source dataset
uspto-grants-2016_03
Patent number
US09284335B2

Reaction notes

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