Pentanenitrile, 4,4-dimethyl-3-oxo- → 2-[3-(3-t-butyl-5-amino-1H-pyrazol-1-yl)phenyl]-1-morpholinoethanone

HRID 16944

反応式

HRID 16944 の反応式
[NH:1]([C:3]1[CH:4]=[C:5]([CH2:9][C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1)[NH2:2].[CH3:18][C:19]([CH3:26])([CH3:25])[C:20](=O)[CH2:21][C:22]#[N:23].C(=O)([O-])O.[Na+]>C(O)C.Cl>[C:19]([C:20]1[CH:21]=[C:22]([NH2:23])[N:1]([C:3]2[CH:4]=[C:5]([CH2:9][C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[O:11])[CH:6]=[CH:7][CH:8]=2)[N:2]=1)([CH3:26])([CH3:25])[CH3:18]

参加物

6

反応物 3

HCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 516892Sodium BicarbonateHCID 218673082-(3-Hydrazinophenyl)-1-morpholin-4-yl-ethanone

生成物 1

HCID 218673452-[3-(3-t-butyl-5-amino-1H-pyrazol-1-yl)phenyl]-1-morpholinoethanone収率 91.6%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 702Ethanol溶媒

実験手順

To a stirred suspension of (3-nitro-phenyl)-acetic acid (2 g) in CH2Cl2 (40 ml, with a catalytic amount of DMF) at 0° C. under N2 was added oxalyl chloride (1.1 ml) drop wise. The reaction mixture was stirred for 40 min morpholine (2.5 g) was added. After stirring for 20 min, the reaction mixture was filtered. The filtrate was concentrated in vacuo to yield 1-morpholin-4-yl-2-(3-nitro-phenyl)-ethanone as a solid (2 g). A mixture of 1-morpholin-4-yl-2-(3-nitro-phenyl)-ethanone (2 g) and 10% Pd on activated carbon (0.2 g) in ethanol (30 ml) was hydrogenated at 30 psi for 3 h and filtered over Celite. Removal of the volatiles in vacuo provided 2-(3-amino-phenyl)-1-morpholin-4-yl-ethanone (1.7 g). A solution of 2-(3-amino-phenyl)-1-morpholin-4-yl-ethanone (1.7 g, 7.7 mmol) was dissolved in 6 N HCl (15 ml), cooled to 0° C., and vigorously stirred. Sodium nitrite (0.54 g) in water (8 ml) was added. After 30 min, tin (II) chloride dihydrate (10 g) in 6 N HCl (30 ml) was added. The reaction mixture was stirred at 0° C. for 3 h. The pH was adjusted to pH 14 with solid potassium hydroxide and extracted with EtOAc. The combined organic extracts were concentrated in vacuo provided 2-(3-hydrazin-phenyl)-1-morpholin-4-yl-ethanone (1.5 g). 2-(3-Hydrazinophenyl)-1-morpholin-4-yl-ethanone (3 g) and 4,4-dimethyl-3-oxopentanenitrile (1.9 g, 15 mmol) in ethanol (60 ml) and 6 N HCl (1 ml) were refluxed for 1 h and cooled to RT. The reaction mixture was neutralized by adding solid sodium hydrogen carbonate. The slurry was filtered and removal of the volatiles in vacuo provided a residue that was extracted with ethyl acetate. The volatiles were removed in vacuo to provide 2-[3-(3-tert-butyl-5-amino-1H-pyrazol-1-yl)phenyl]-1-morpholinoethanone (4 g), which was used without further purification.

後処理

  1. filtrationThe slurry was filtered
  2. customremoval of the volatiles in vacuo
  3. customprovided a residue that
  4. extractionwas extracted with ethyl acetate
  5. customThe volatiles were removed in vacuo

出典と根拠

ORDレコード
ord-67ab6ba2131540f0a9bd0d9dd276eb2f
出典データセット
uspto-grants-2010_06
特許番号
US07737283B2

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