HRID1431153

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID10796

Cesium carbonate

CCs2O3

结构：CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21

HCID636044

1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

C39H32OP2

结构：CC(=O)OCc1c(-c2cc(Br)c(=O)n(C)n2)cccc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O

HCID66742192

未命名化合物

HCID66743079

未命名化合物

PRODUCTS

生成物

结构：CC(=O)OCc1c(-c2cc(Nc3ccc(N4C[C@@H]5C[C@H]4CN5C)nn3)c(=O)n(C)n2)cccc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O

HCID66743398

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

结构：O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Pd].[Pd]

催化剂HCID9811564

Bis(dibenzylideneacetone)palladium

C51H42O3Pd2

CONDITIONS

反应条件

温度: 100 °C

PROCEDURE

实验过程

6-((1S,4S)-5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyridazin-3-ylamine (100 mg, 0.487 mmol, Eq: 1.00), acetic acid 2-(5-bromo-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester (284 mg, 0.512 mmol, Eq: 1.05), xantphos (42.3 mg, 0.073 mmol, Eq: 0.15), tris(dibenzylideneacetone)-dipalladium (0) (33.5 mg, 0.036 mmol, Eq: 0.075) and cesium carbonate (476 mg, 1.46 mmol, Eq: 3.00) were added to a microwave vial. The vial was capped and purged. Degassed dioxane (about 5 ml) was added through a syringe and the vial was purged again and back filled with nitrogen. The reaction was heated at 100° C. overnight in a sand bath. The reaction was filtered through celite and concentrated. The crude product was purified by chromatography using a gradient of 0% to 25% methanol in DCM. LCMS and NMR showed major impurities. Took on to next step without further purification.

WORKUP

后处理

customThe vial was capped
custompurged
additionDegassed dioxane (about 5 ml) was added through a syringe
customthe vial was purged again
additionback filled with nitrogen
filtrationThe reaction was filtered through celite
concentrationconcentrated
customThe crude product was purified by chromatography
customTook on to next step without further purification

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-41c79ba0c8eb45608435530ccce6d75a
来源数据集: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08940741B2
来源说明: uspto-grants-2015_01

反应 SMILES

[CH3:1][N:2]1[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[C:9]1[N:14]=[N:13][C:12]([NH2:15])=[CH:11][CH:10]=1.Br[C:17]1[C:22](=[O:23])[N:21]([CH3:24])[N:20]=[C:19]([C:25]2[CH:35]=[CH:34][CH:33]=[C:32]([N:36]3[N:45]=[CH:44][C:43]4[C:38](=[C:39]([F:50])[CH:40]=[C:41]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:42]=4)[C:37]3=[O:51])[C:26]=2[CH2:27][O:28][C:29](=[O:31])[CH3:30])[CH:18]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:46]([C:41]1[CH:42]=[C:43]2[C:38](=[C:39]([F:50])[CH:40]=1)[C:37](=[O:51])[N:36]([C:32]1[CH:33]=[CH:34][CH:35]=[C:25]([C:19]3[CH:18]=[C:17]([NH:15][C:12]4[N:13]=[N:14][C:9]([N:5]5[CH2:4][C@@H:3]6[CH2:8][C@H:6]5[CH2:7][N:2]6[CH3:1])=[CH:10][CH:11]=4)[C:22](=[O:23])[N:21]([CH3:24])[N:20]=3)[C:26]=1[CH2:27][O:28][C:29](=[O:31])[CH3:30])[N:45]=[CH:44]2)([CH3:47])([CH3:48])[CH3:49]