HRID276950

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID24758

Sodium hydride

HNa

HCID2773685

tert-Butyl diethylphosphonoacetate

C10H21O5P

结构：O=C1CCCCC1n1nc(-c2c(-c3ccccc3)nn3ccccc23)ccc1=O

HCID11069041

3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

C23H20N4O2

PRODUCTS

生成物

结构：CC(C)(C)OC(=O)CC1=C(n2nc(-c3c(-c4ccccc4)nn4ccccc34)ccc2=O)CCCC1

HCID11113637

未命名化合物

$结构：CC(C)(C)OC(=O)/C=C1\CCCCC1n1nc(-c2c(-c3ccccc3)nn3ccccc23)ccc1=O$

HCID15870061

未命名化合物

结构：CC(C)(C)OC(=O)CC1=CCCCC1n1nc(-c2c(-c3ccccc3)nn3ccccc23)ccc1=O

HCID15870062

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID1140

Toluene

C7H8

PROCEDURE

实验过程

To a suspension of sodium hydride (44.2 g, 60% oil) in toluene (5.6 l) was added carefully tert-butyl (diethoxyphosphoryl)acetate (278.3 g) at 0° C. under nitrogen atmosphere. After being stirred for 30 minutes, to a reaction mixture was added by portions 3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (282.7 g), and which was stirred for additional 68 hours at ambient temperature. A reaction mixture was poured into ice-water (3 l) and organic layer was separated. Aqueous layer was reextracted with ethyl acetate (2 l). Organic layer was combined, washed In turn with water (2 l×3) and saturated sodium chloride in water, and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (270-400 mesh, 7 Kg) eluting in turn with 9%, 17% and 33% ethyl acetate in toluene. Fractions containing another isomer were further purified under the same conditions (silica gel 1 kg). Fractions containing each of desired products were collected and concentrated in vacuo to give 3-[2-{2-(tert-butoxycarbonylmethyl)-1-cyclohexenyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo-[1,5-a]pyridine (252.9 g), 3-[2-{2-(tert-butoxycarbonylmethyl)-2-cyclohexen-1-yl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (31.68 g) and (E)-3-[2-{2-(tert-butoxycarbonylmethylene)cyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (16.08 g) respectively.

WORKUP

后处理

stirringwas stirred for additional 68 hours at ambient temperature
customwas separated
washwashed In turn with water (2 l×3) and saturated sodium chloride in water
dry with materialdried over magnesium sulfate
customEvaporation of the solvent
customgave a residue, which
customwas chromatographed on silica gel (270-400 mesh, 7 Kg)
washeluting in turn with 9%, 17% and 33% ethyl acetate in toluene
additionFractions containing another isomer
customwere further purified under the same conditions (silica gel 1 kg)
additionFractions containing each of desired products
customwere collected
concentrationconcentrated in vacuo

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-8733843503f34f8bb3f9f8a8b99bcaf2
来源数据集: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
专利: US06355640B1
来源说明: uspto-grants-2002_03

反应 SMILES

[H-].[Na+].C(OP([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(OCC)=O)C.O=[C:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[N:26]1[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]2[C:34]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[N:35][N:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=23)=[N:27]1>C1(C)C=CC=CC=1>[C:15]([O:14][C:12]([CH2:11][C:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=1[N:26]1[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]2[C:34]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[N:35][N:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=23)=[N:27]1)=[O:13])([CH3:16])([CH3:17])[CH3:18].[C:15]([O:14][C:12]([CH2:11][C:20]1[CH:21]([N:26]2[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]3[C:34]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[N:35][N:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=34)=[N:27]2)[CH2:22][CH2:23][CH2:24][CH:25]=1)=[O:13])([CH3:16])([CH3:17])[CH3:18].[C:15]([O:14][C:12](/[CH:11]=[C:20]1/[CH:21]([N:26]2[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]3[C:34]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[N:35][N:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=34)=[N:27]2)[CH2:22][CH2:23][CH2:24][CH2:25]/1)=[O:13])([CH3:16])([CH3:17])[CH3:18]