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

HRID 1445730노트

반응식

HRID 1445730 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 702Ethanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fb689b64f94741c9b95d5fc76bb24895
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07666895B2

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