Water → HCID 118006195、化合物

HRID 926584

反応式

HRID 926584 の反応式
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17](I)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[C:27]([CH:35]1[CH2:40][CH2:39][N:38]([C:41](=[O:43])[CH3:42])[CH2:37][CH2:36]1)(=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:27]([OH:34])([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:35]3[CH2:40][CH2:39][N:38]([C:41](=[O:43])[CH3:42])[CH2:37][CH2:36]3)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1

参加物

7

反応物 4

HCID 962WaterHCID 5234Sodium ChlorideHCID 27407141-Acetyl-4-benzoylpiperidine2 回HCID 1180061563-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-6-iodo-2-methoxyquinoline2 回

生成物 1

HCID 118006195HCID 118006195、化合物

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
23 °C

実験手順

A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.73 mL, 0.94 mmol) was added dropwise to an ice-water cooled, stirring solution of 3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-6-iodo-2-methoxyquinoline (300 mg, 0.63 mmol, Intermediate 20: step c) in dry tetrahydrofuran (6 mL). After 10 minutes, a solution of 1-(4-benzoylpiperidin-1-yl)ethanone (218 mg, 0.94 mmol, Intermediate 18) in tetrahydrofuran (5 mL) was added dropwise. After 30 minutes, the flask was warmed to 23° C. After 1 hour, the flask was warmed to 55° C. After 30 minutes, the flask was allowed to cool to 23° C. Water (20 mL), saturated aqueous sodium chloride solution (20 mL), and ethyl acetate (100 mL) were added. The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash column chromatography purification. Elution with dichloromethane initially, grading to 5% methanol-dichloromethane provided the title compound which was further purified by RP-HPLC eluting initially with 5% acetonitrile-water (containing 0.05% trifluoroacetic acid), grading to 95% acetonitrile-water (containing 0.05% trifluoroacetic acid) to provide the title compound as a white solid after partitioning the purified material between dichloromethane-saturated aqueous sodium bicarbonate solution, separating the layers, drying the organic layer with sodium sulfate, filtering the dried solution, and concentrating the filtrate to dryness. 1H NMR (500 MHz, CDCl3) δ ppm 8.47 (s, 1H), 8.32-8.25 (m, 1H), 8.06 (s, 1H), 7.80-7.72 (m, 1H), 7.72-7.62 (m, 1H), 7.57-7.48 (m, 4H), 7.44-7.38 (m, 2H), 7.37-7.29 (m, 2H), 7.26-7.18 (m, 1H), 4.75-4.63 (m, 1H), 4.34 (s, 2H), 4.05 (s, 3H), 3.90-3.75 (m, 1H), 3.17-2.99 (m, 1H), 2.76 (t, J=11.8 Hz, 1H), 2.66-2.49 (m, 1H), 2.28 (s, 1H, rotamer), 2.27 (s, 1H, rotamer), 2.05 (s, 3H, rotamer), 2.04 (s, 3H, rotamer), 1.75-1.62 (m, 1H), 1.55-1.28 (m, 3H); MS (ESI): mass calcd. for C33H32ClN5O3, 581.2. m/z found, 582.0 [M+H]+.

後処理

  1. temperaturecooled
  2. waitAfter 30 minutes
  3. waitAfter 1 hour
  4. temperaturethe flask was warmed to 55° C
  5. waitAfter 30 minutes
  6. temperatureto cool to 23° C
  7. customThe layers were separated
  8. dry with materialThe organic layer was dried with sodium sulfate
  9. filtrationthe dried solution was filtered
  10. additionSilica gel (5 g) was added to the filtrate
  11. concentrationthe mixture was concentrated by rotary evaporation
  12. customto afford a free-flowing powder
  13. customThe powder was loaded onto a silica gel column for flash column chromatography purification
  14. washElution with dichloromethane initially

出典と根拠

ORDレコード
ord-9f5ee6b667eb4b3bb41672de4c45e529
出典データセット
uspto-grants-2016_03
特許番号
US09284308B2

関連ノート

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