Potassium hydroxy sulfite → N-(4-((4-(3-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-(methylsulfinyl)acetamide

HRID 2069024ノート

反応式

HRID 2069024 の反応式
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:37])[NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:36])[CH2:33][S:34][CH3:35])[CH:26]=3)=[CH:15][CH:14]=2)[N:7]([C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:45]OS([O-])=O.[K+]>CN(C=O)C.O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:37])[NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:36])[CH2:33][S:34]([CH3:35])=[O:45])[CH:26]=3)=[CH:15][CH:14]=2)[N:7]([C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

4

反応物 2

HCID 23707502Potassium hydroxy sulfite2 回HCID 45257074N-(4-((4-(3-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-(methylthio)acetamide

生成物 1

HCID 53241901N-(4-((4-(3-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-(methylsulfinyl)acetamide収率 58.7%

試薬・触媒・溶媒 1

HCID 21962138N,N-Dimethylformamide--water (1/1)溶媒

実験手順

To a solution of N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-(methylthio)acetamide (Example 19) (20 mg, 0.03 mmol) in a mixture of DMF/H2O (1:1 v/v, 1.0 mL) was added Oxone (10 mg, 0.03 mmol) and the reaction was stirred at RT for 3 days. A second portion of Oxone® (10 mg, 0.03 mmol) was added, the mixture was stirred for a further 24 hr and was then partitioned between brine (20 mL) and DCM (20 mL). The organic extract was washed with brine (20 mL), dried (MgSO4) and evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 4 g, 30-100% EtOAc in isohexane, gradient elution) and subjected to SCX capture and release to afford the title compound (Example 20) as a tan coloured solid (11 mg, 52%): m/z 625 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.39 (3H, s), 2.69 (3H, s), 3.88 (2H, d), 4.04 (2H, d) 5.39 (2H, s), 6.35 (1H, s), 7.02 (1H, d), 7.31 (1H, dd), 7.36 (2H, m), 7.44 (2H, m), 7.58-7.64 (3H, overlapping m), 7.93 (1H, m), 8.30-8.33 (2H, overlapping m), 8.37 (1H, d), 8.59 (1H, br s), 8.79 (1H, br s), 10.85 (1H, br s).

後処理

  1. stirringthe mixture was stirred for a further 24 hr
  2. customwas then partitioned between brine (20 mL) and DCM (20 mL)
  3. extractionThe organic extract
  4. washwas washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customthe residue was purified by flash column chromatography (SiO2, 4 g, 30-100% EtOAc in isohexane, gradient elution)

出典と根拠

ORDレコード
ord-b20417b1aef341b99f0e5b14f1f29aa2
出典データセット
uspto-grants-2012_10
特許番号
US08299073B2

反応ノート

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