Methane → (2R)-1-[3-(2-{[2-(2-dimethylaminoethoxy)-3-pyridinyl]oxy}ethoxy)-2-pyrazinyl]-2-methylpiperazine

HRID 1247632

反応式

HRID 1247632 の反応式
Cl[C:2]1[C:3]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]2[CH3:14])=[N:4][CH:5]=[CH:6][N:7]=1.C.[CH3:16][N:17]([CH3:31])[CH2:18][CH2:19][O:20][C:21]1[C:26]([O:27][CH2:28][CH2:29][OH:30])=[CH:25][CH:24]=[CH:23][N:22]=1.C1COCC1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[CH3:16][N:17]([CH3:31])[CH2:18][CH2:19][O:20][C:21]1[C:26]([O:27][CH2:28][CH2:29][O:30][C:2]2[C:3]([N:8]3[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]3[CH3:14])=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:25][CH:24]=[CH:23][N:22]=1

参加物

6

反応物 4

HCID 297MethaneHCID 9992195(R)-2-Chloro-3-(2-methylpiperazin-1-YL)pyrazineHCID 117083962-{[2-(2-Dimethylaminoethoxy)-3-pyridinyl]oxy}ethanolHCID 66863523KOtBu THF

生成物 1

HCID 9870582(2R)-1-[3-(2-{[2-(2-dimethylaminoethoxy)-3-pyridinyl]oxy}ethoxy)-2-pyrazinyl]-2-methylpiperazine

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

(2R)-1-(3-chloro-2-pyrazinyl)-2-methylpiperazine (20 L in toluene solution; see Example 8 for preparation) and active charcoal (201 g) was added to the 328 L-reactor containing 2-{[2-(2-dimethylaminoethoxy)-3-pyridinyl]oxy} ethanol (Example 1C) in toluene solution. The mixture was stirred for 25 minutes before transferred to a through a GAF-filter (containing a Teflon filter bag) to a 250 L-stainless steel reactor. The mixture was heated to 100° C. before the prepared “THF/potassium tert-butoxide-solution” was added to the reactor using a 50 L addition bowl. After 10 L “THF/potassium tert-butoxide-solution” was added, an IP-HPLC was taken to ensure that the title compound had started to form. The total addition of THF/potassium tert-butoxide-solution was made during 2 h and 15 minutes. Water (21 L) and sodium chloride (1 kg) was added to a 198 L-glasslined reactor. The salt was dissolved before the reaction mixture was transferred from the 328 L-reactor and quenched into the 198 L-reactor. Toluene (10 L) was also transferred to make sure that no reaction-mixture was left in the hoses used for the transfer. The mixture was then heated to 70° C. before the mechanical stirrer was turned off. The phases were allowed to separate for 30 minutes before the water phase (25 L) was discharged. The mixture was heated to reflux and toluene (10 L) was distilled off. Water (100 L) was added and the mixture was heated to reflux again and 60 L of water was distilled off. The remaining solution was then cooled to RT. The title compound was never isolated; it was directly used in the next step (Example 3C). IP sample (HPLC) of the toluene mixture confirmed the retention time for the desired product (tret=2.2 minutes).

後処理

  1. filtrationfilter bag) to a 250 L-stainless steel reactor
  2. customprepared “THF/potassium tert-butoxide-solution”
  3. additionwas added to the reactor
  4. additiona 50 L addition bowl

出典と根拠

ORDレコード
ord-68fa078e4bf0498b9a38233b399aecde
出典データセット
uspto-grants-2006_10
特許番号
US07129354B2

関連ノート

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