Cesium fluoride → (7RS,9aRS)-[2-(7-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol

HRID 1172558Notes

Reaction equation

HRID 1172558 reaction equation
Cl[C:2]1[CH: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[N: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[N: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)[CH:7]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 10035034((7R,9AS)-Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanolHCID 713667695-Chloro-2-(furan-2-YL)-[1,2,4]triazolo[1,5-A]pyrimidin-7-amine

Product 1

HCID 11773072(7RS,9aRS)-[2-(7-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

5-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamine (1 eq; see WO 99/43678 A1), 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 100° 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 7.69 (d, J=2.3 Hz, 1H), 7.10 (d, J=3.5 Hz, 1H), 6.61 (dd, J=3.5, 2.3 Hz, 1H), 5.73 (s, 1H), 4.32 (d, J=13.5 Hz, 1H), 4.24 (d, J=13.5 Hz, 1H), 3.82 (dd, J=10.5, 7.5 Hz, 1H), 3.74 (dd, J=10.5, 7.5 Hz, 1H), 3.10 (dt, J=12.5, 3.2 Hz, 1H), 2.94 (d, J=11.5 Hz, 1H), 2.79 (d, J=11.5 Hz, 1H), 2.67 (dd, J=13.0, 10.5 Hz, 1H), 2.21 (m, 2H), 1.96 (m, 1H), 1.85 (brd, 12.0 Hz, 2H), 1.60 (m, 1H), 1.47 (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

Sources & evidence

ORD record
ord-47a05224edbf4ff9aec6b8fc124229c0
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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