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 926114

반응식

HRID 926114 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-83c8a21b0d114c889a9e44d629030d32
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284335B2

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