Diphosgene → tert-Butyl 4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)-2-methylpropyl)pyridin-2-ylcarbamate

HRID 1916814ノート

反応式

HRID 1916814 の反応式
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:18]([O-])(O)=[O:19].[Na+].ClC(OC(Cl)=O)(Cl)Cl.[NH2:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]([O:42][C:43]([CH3:60])([CH3:59])[CH2:44][C:45]2[CH:50]=[CH:49][N:48]=[C:47]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[CH:46]=2)=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O.O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:18](=[O:19])[NH:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]([O:42][C:43]([CH3:60])([CH3:59])[CH2:44][C:45]3[CH:50]=[CH:49][N:48]=[C:47]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:55])([CH3:57])[CH3:56])[CH:46]=3)=[CH:34][CH:33]=2)[N:7]([C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 5

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 67359542tert-Butyl 4-(2-(4-aminonaphthalen-1-yloxy)-2-methylpropyl)pyridin-2-ylcarbamate

生成物 1

HCID 58416777tert-Butyl 4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)-2-methylpropyl)pyridin-2-ylcarbamate収率 14%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (4) (WO 2000043384) (250 mg, 1.090 mmol) in DCM (25 mL) was added a saturated solution of aq NaHCO3 (17 mL), and the mixture was stirred vigorously. The mixture was cooled to 0° C. and then trichloromethylchloroformate (395 μl, 3.27 mmol) was added in one portion. The resulting mixture was stirred at 0° C. for 90 min. The layers were then separated, the organic extract was dried and the solvents removed under reduced pressure to afford a brown-orange oil, which was dried under high vacuum, at 30° C. for 30 min. The resulting oil was then taken up in THF (4.0 mL), and was added to tert-butyl 4-(2-(4-aminonaphthalen-1-yloxy)-2-methylpropyl)pyridin-2-ylcarbamate (28) (92 mg, 0.23 mmol). DIPEA (118 μl, 0.677 mmol) was then added, and the reaction mixture was stirred at RT over 17 hr. Water (15 mL) and EtOAc (15 mL) were added to the purple mixture and the layers separated. The aqueous layer was extracted with EtOAc (10 mL). The combined organic extracts were washed with brine (20 mL), dried and the solvents removed under reduced pressure. The crude material was purified by column chromatography (40 g) eluting with 0 to 50% EtOAc in iso-hexane, to give tert-butyl 4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)-2-methylpropyl)pyridin-2-ylcarbamate (29) (24 mg, 14%) as a purple foam: m/z 663 (M+H)+ (ES+).

後処理

  1. stirringThe resulting mixture was stirred at 0° C. for 90 min
  2. customThe layers were then separated
  3. extractionthe organic extract
  4. customwas dried
  5. customthe solvents removed under reduced pressure
  6. customto afford a brown-orange oil, which
  7. customwas dried under high vacuum, at 30° C. for 30 min
  8. stirringthe reaction mixture was stirred at RT over 17 hr
  9. customthe layers separated
  10. extractionThe aqueous layer was extracted with EtOAc (10 mL)
  11. washThe combined organic extracts were washed with brine (20 mL)
  12. customdried
  13. customthe solvents removed under reduced pressure
  14. customThe crude material was purified by column chromatography (40 g)
  15. washeluting with 0 to 50% EtOAc in iso-hexane

出典と根拠

ORDレコード
ord-ae09f925d8d34ebfaa0fc9efe31a20d1
出典データセット
uspto-grants-2013_12
特許番号
US08618140B2

反応ノート

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