Triethylamine → 2-Furan-2-yl-5-[5-(5-methyl-isoxazol-3-ylmethyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine

HRID 1172567노트

반응식

HRID 1172567 반응식
[CH3:1][C:2]1[O:6][N:5]=[C:4]([CH2:7]O)[CH:3]=1.CCN(CC)CC.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[CH:26]12[CH2:32][CH:29]([NH:30][CH2:31]1)[CH2:28][N:27]2[C:33]1[N:38]=[C:37]([NH2:39])[N:36]2[N:40]=[C:41]([C:43]3[O:44][CH:45]=[CH:46][CH:47]=3)[N:42]=[C:35]2[N:34]=1>C(Cl)Cl.CC#N>[O:44]1[CH:45]=[CH:46][CH:47]=[C:43]1[C:41]1[N:42]=[C:35]2[N:34]=[C:33]([N:27]3[CH2:28][CH:29]4[CH2:32][CH:26]3[CH2:31][N:30]4[CH2:7][C:4]3[CH:3]=[C:2]([CH3:1])[O:6][N:5]=3)[N:38]=[C:37]([NH2:39])[N:36]2[N:40]=1

참가 물질

8

반응물 5

HCID 8471Triethylamine2회HCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 2736567(5-Methyl-1,2-oxazol-3-yl)methanolHCID 686848935-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine

생성물 1

HCID 114521722-Furan-2-yl-5-[5-(5-methyl-isoxazol-3-ylmethyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

In a separate flask, (5-methyl-isoxazol-3-yl)-methanol (32 mg, 0.28 mmol) was dissolved in 4 mL of CH2Cl2 along with 1.3 eq. of Et3N. The solution was cooled in an ice bath and methanesulfonyl chloride (1.2 eq) was added. The reaction mixture was warmed to room temperature and stirred for 45 minutes. It was then quenched with brine and the two layers were separated. The organic layer was dried with Na2SO4 and concentrated under reduced pressure to afford the mesylated derivative. This mesylate was then added to a solution containing 5-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (0.14 mmol; see subpart (a) above), and Et3N (0.3 mmol) in 3 mL of CH3CN. The resulting reaction mixture was stirred at room temperature for 18 hours. It was then concentrated and purified by preparative HPLC to afford 2-furan-2-yl-5-[5-(5-methyl-isoxazol-3-ylmethyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine. 1H NMR (400 Hz, DMSO-d6) δ 8.20 (brs, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.00 (d, J=3.6 Hz, 1H), 6.60 (dd, J=3.6, 1.0 Hz, 1H), 6.30 (s, 1H), 4.80 (brs, 2H), 4.20-4.30 (m, 8H), 2.35 (s, 3H), 2.30 (m, 1H). MS m/z: 394 [M+H]+.

후처리

  1. temperatureThe solution was cooled in an ice bath
  2. customIt was then quenched with brine
  3. customthe two layers were separated
  4. dry with materialThe organic layer was dried with Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford the mesylated derivative
  7. customThe resulting reaction mixture
  8. stirringwas stirred at room temperature for 18 hours
  9. concentrationIt was then concentrated
  10. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-e0e60a53aad74891af1a4ab144af17dd
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834014B2

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