Cesium fluoride → [2-[5-Amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-7-yl]methanol

HRID 1172557Notes

Reaction equation

HRID 1172557 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]2[N:9]=[C:10]([C:12]3[O:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:4]2[CH:3]=1.[CH2:17]1[NH:22][CH2:21][CH2:20][N:19]2[CH2:23][C@H:24]([CH2:27][OH:28])[CH2:25][CH2:26][C@@H:18]12.[F-].[Cs+]>CS(C)=O>[NH2:8][C:6]1[N:5]2[N:9]=[C:10]([C:12]3[O:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:4]2[CH:3]=[C:2]([N:22]2[CH2:21][CH2:20][N:19]3[CH2:23][CH:24]([CH2:27][OH:28])[CH2:25][CH2:26][CH:18]3[CH2:17]2)[N:7]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 99427675-Amino-7-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]pyrimidineHCID 10035034((7R,9AS)-Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 11222433[2-[5-Amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-7-yl]methanol

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

7-Chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]pyrimidin-5-ylamine (1 eq, see U.S. Pat. No. 6,222,035 B1), cis-(octahydro-pyrido[1,2-a]pyrazin-7-yl)-methanol (1-2 eq.), and CsF (1-2 eq.) were dissolved in DMSO. The mixture was stirred at around 120° C. for 18 hours. The solution was then cooled to room temperature, filtered and purified by preparative HPLC using aqueous CH3CN (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 7.71 (d, J=2.0 Hz, 1H), 7.14 (d, J=3.5 Hz, 1H), 6.63 (dd, J=3.5, 2.0 Hz, 1H), 5.99 (s, 1H), 4.26 (d, J=13.5 Hz, 1H), 4.19 (d, J=13.5 Hz, 1H), 3.83 (dd, J=10.5, 7.5 Hz, 1H), 3.74 (dd, J=10.5, 7.5 Hz, 1H), 3.04 (dt, J=12.5, 3.0 Hz, 1H), 2.95 (d, J=12.0 Hz, 1H), 2.80 (d, J=11.0 Hz, 1H), 2.62 (dd, J=12.5, 10.5 Hz, 1H), 2.22 (m, 2H), 1.98 (m, 1H), 1.86 (brd, 12.0 Hz, 2H), 1.62 (m, 1H), 1.50-1.42 (m, 2H). MS m/z: 370 [M+H]+.

Workup

  1. temperatureThe solution was then cooled to room temperature
  2. filtrationfiltered
  3. custompurified by preparative HPLC
  4. customto give the
  5. customAlternatively, for scale up synthesis
  6. customthe DMSO solvent was removed
  7. customthe crude product was chromatographed on silica gel column

Sources & evidence

ORD record
ord-1da7287fe27f4a479fb940bdd7a02ad6
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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