2-(Furan-2-yl)-5-(methylsulfonyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amine → (7RS,9aRS)-[2-(7-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol

HRID 1172556Notes

Reaction equation

HRID 1172556 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:19]=[C:9]2[N:10]=[C:11](S(C)(=O)=O)[N:12]=[C:13]([NH2:14])[N:8]2[N:7]=1.[CH2:20]1[NH:25][CH2:24][CH2:23][N:22]2[CH2:26][C@H:27]([CH2:30][OH:31])[CH2:28][CH2:29][C@@H:21]12>CS(C)=O>[NH2:14][C:13]1[N:8]2[N:7]=[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)[N:19]=[C:9]2[N:10]=[C:11]([N:25]2[CH2:24][CH2:23][N:22]3[CH2:26][CH:27]([CH2:30][OH:31])[CH2:28][CH2:29][CH:21]3[CH2:20]2)[N:12]=1

Participants

4

Reactant 2

HCID 99708822-(Furan-2-yl)-5-(methylsulfonyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amineHCID 10035034((7R,9AS)-Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 11268712(7RS,9aRS)-[2-(7-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

2-Furan-2-yl-5-methanesulfonyl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (1 eq.; for reference, see J. Chem. Soc. Perkin Trans. 1, 801 (1995)) and cis-(octahydro-pyrido[1,2-a]pyrazin-7-yl)-methanol (1-2 eq; see U.S. Pat. No. 5,122,525) were dissolved in DMSO. The mixture was stirred at around 80° C. for 2 hours. The solution was then cooled to room temperature, filtered and purified by preparative HPLC using aqueous CH3CN solution (buffered with 0.1% TFA) to give the desired compound as a white solid. Alternatively, for scale up synthesis, the DMSO solvent was removed and the crude product was chromatographed on silica gel column using 5-10% MeOH/CH2Cl2 as eluant to afford the desired product. 1H NMR (400 Hz, CD3OD) δ 7.70 (d, J=2.0 Hz, 1H), 7.12 (d, J=3.5 Hz, 1H), 6.62 (dd, J=3.5, 2.0 Hz, 1H), 4.75 (d, J=12.0 Hz, 1H), 4.65 (d, J=12.5 Hz, 1H), 3.82 (dd, J=10.5, 7.5 Hz, 1H), 3.74 (dd, J=10.5, 7.5 Hz, 1H), 3.11 (dt, J=13.0, 3.0 Hz, 1H), 2.93 (d, J=11.5 Hz, 1H), 2.78 (d, J=11.5 Hz, 1H), 2.68 (dd, J=13.0, 10.5 Hz, 1H), 2.22 (dd, J=11.5, 3.0 Hz, 1H), 2.14 (dt, J=12.0, 3.0 Hz, 1H), 1.93 (m, 1H), 1.85 (brd, J=12.0 Hz, 2H), 1.60 (m, 1H), 1.43 (m, 2H). MS m/z: 371 [M+H]+.

Workup

  1. temperatureThe solution was then cooled to room temperature
  2. filtrationfiltered
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-9f06de32cc024a498095d9dd94b273a0
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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