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 1172567Notes

Reaction equation

HRID 1172567 reaction equation
[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

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 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

Product 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

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-e0e60a53aad74891af1a4ab144af17dd
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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