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 1172557ノート

反応式

HRID 1172557 の反応式
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

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
120 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-1da7287fe27f4a479fb940bdd7a02ad6
出典データセット
uspto-grants-2010_11
特許番号
US07834014B2

反応ノート

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