Water → N-(3-Chloro-4-methoxy-phenyl)-N'-cycloheptyl-N''-methyl-N''-(1-methyl-piperidin-4-yl)-[1,3,5]triazine-2,4,6-triamine

HRID 916102

반응식

HRID 916102 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([Cl:17])[CH:10]=2)[N:5]=[C:4]([NH:18][CH:19]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:3]=1.[CH3:26][NH:27][CH:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1.[OH-].[Na+].O>O1CCOCC1.C(Cl)Cl>[Cl:17][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[N:5]=[C:4]([NH:18][CH:19]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[N:3]=[C:2]([N:27]([CH3:26])[CH:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)[N:7]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH3:16]

참가 물질

7

반응물 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 5663231-Methyl-4-(methylamino)piperidineHCID 218970216-chloro-N-(3-chloro-4-methoxyphenyl)-N'-cycloheptyl-[1,3,5]triazine-2,4-diamine

생성물 1

HCID 21896974N-(3-Chloro-4-methoxy-phenyl)-N'-cycloheptyl-N''-methyl-N''-(1-methyl-piperidin-4-yl)-[1,3,5]triazine-2,4,6-triamine수율 30.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매2회

실험 절차

To 133 (10.014 g, 26.2 mmol) in 1,4-dioxane (80 mL) was added slowly methyl-(1-methyl-piperidin-4-yl)-amine (3.8 mL, 26.2 mmol) dissolved in 1,4-dioxane (15 mL) by addition funnel. Then aqueous sodium hydroxide (10.5 mL, 2.5 N, 26.2 mmol) was added by addition funnel followed by water (26 mL). The reaction mixture was heated at reflux for about 2.5 hours under a nitrogen atmosphere. The reaction was cooled and diluted with methylene chloride. The reaction mixture was filtered using vacuum and the white solid 147 removed. The filtrate was then washed 1 time with brine. The aqueous layer was back extracted 1 time with methylene chloride. The organic layers were combined and dried over potassium carbonate. The organic solution was filtered and concentrated in vacuo to afford the crude product (5.89 g). The crude reaction product was purified by flash column chromatography (silica gel) eluting with 96:3:1 methylene chloride:methanol:15 M ammonium hydroxide. The fractions were combined, dried over sodium sulfate/potassium carbonate, filtered, and concentrated in vacuo to afford 137 as a white solid (3.84 g, 30.9%), mp 104-105° C.; HPLC: YMC Pack Pro C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2): CH3OH:CH3CN], 264 nm, Rt 13.8 min, 97% purity); MS (ESI): m/z 474 (M+H, 41), 408 (2.3), 364 (2.8), 258 (13), 239 (14), 239 (47.5), 238 (100), 127 (5.3).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for about 2.5 hours under a nitrogen atmosphere
  3. temperatureThe reaction was cooled
  4. filtrationThe reaction mixture was filtered
  5. customthe white solid 147 removed
  6. washThe filtrate was then washed 1 time with brine
  7. extractionThe aqueous layer was back extracted 1 time with methylene chloride
  8. dry with materialdried over potassium carbonate
  9. filtrationThe organic solution was filtered
  10. concentrationconcentrated in vacuo
  11. customto afford the crude product (5.89 g)
  12. customThe crude reaction product
  13. customwas purified by flash column chromatography (silica gel)
  14. washeluting with 96:3:1 methylene chloride
  15. dry with materialdried over sodium sulfate/potassium carbonate
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-59de31c8b9b741aabb383e0f95272e0b
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07268134B2

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