HRID926626

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID25517

未命名化合物

HCID18522661

未命名化合物

结构：Cn1cncc1C(=O)C1CCN(C(=O)OC(C)(C)C)CC1

HCID66677755

未命名化合物

2 次

结构：FC(F)(F)c1nc2ccc(Br)cc2c(Cl)c1Cc1ccccc1

HCID118006336

未命名化合物

2 次

HCID178418339

Butyllithium

C4H9Li

PRODUCTS

生成物

HCID6422

未命名化合物

结构：CC(=O)N1CCC(C(O)(c2ccc3nc(C(F)(F)F)c(Cc4ccccc4)c(Cl)c3c2)c2cncn2C)CC1.O=C(O)C(F)(F)F

HCID131735027

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID8028

Tetrahydrofuran

C4H8O

CONDITIONS

反应条件

温度: -78 °C

PROCEDURE

实验过程

A mixture of 3-benzyl-6-bromo-4-chloro-2-(trifluoromethyl)quinoline (632 mg, 1.58 mmol, Intermediate 72: step b), 1-(4-(1-methyl-1H-imidazole-5-carbonyl)piperidin-1-yl)ethanone (371 mg, 1.58 mmol, Intermediate 58: step c), and 15 mL of THF was sparged with N2 and cooled to −78° C. To the mixture was added n-BuLi (1.6 M in hexanes, 2.6 mL, 4.2 mmol) dropwise. The reaction mixture was stirred at −78° C. for 10 minutes, then the acetone-dry ice bath was replaced with a water-ice bath. Stirring was continued for 20 minutes at 4° C. Saturated NH4Cl (aq) was added and the organic layer was separated. The aqueous layer was extracted with dichloromethane. The combined organic phases were dried (Na2SO4), filtered, and concentrated to dryness. The crude material was purified by flash column chromatography (silica gel, 0-10% MeOH in DCM) followed by reverse phase HPLC (water/acetonitrile/0.1% TFA) to afford the title compound as a TFA salt. 1H NMR (400 MHz, MeOH-d4, ˜1:1 mixture of rotamers) δ 8.84 (s, 1H), 8.51 (d, J=9.09 Hz, 1H), 8.24 (d, J=9.09 Hz, 1H), 8.07 (s, 1H), 7.78 (d, J=9.09 Hz, 1H), 7.21-7.29 (m, 2H), 7.15-7.21 (m, 1H), 7.01 (d, J=7.07 Hz, 2H), 4.65 (d, J=13.14 Hz, 0.5H), 4.57 (s, 2H), 4.45 (d, J=13.14 Hz, 0.5H), 4.03 (d, J=13.64 Hz, 0.5H), 3.84 (d, J=14.15 Hz, 0.5H), 3.59 (s, 1.5H), 3.57 (s, 1.5H), 3.23-3.32 (m, overlapping with solvent), 3.03 (td, J=2.02, 13.14 Hz, 0.5H), 2.66-2.82 (m, 1H), 2.53 (td, J=2.53, 13.64 Hz, 0.5H), 2.09-2.24 (m, 1H), 2.07 (s, 1.5H), 2.02 (s, 1.5H), 1.41-1.60 (m, 1H), 1.26-1.39 (m, 1H), 1.11-1.26 (m, 1H), 1.05 (d, J=13.14 Hz, 0.5H); MS m/e 557.1 [M+H]+.

WORKUP

后处理

customwas sparged with N2
stirringStirring
waitwas continued for 20 minutes at 4° C
customthe organic layer was separated
extractionThe aqueous layer was extracted with dichloromethane
dry with materialThe combined organic phases were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated to dryness
customThe crude material was purified by flash column chromatography (silica gel, 0-10% MeOH in DCM)

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-adb848f3cb2a48e182843df4fbd945e9
来源数据集: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
专利: US09284308B2
来源说明: uspto-grants-2016_03

反应 SMILES

[CH2:1]([C:8]1[C:9]([C:20]([F:23])([F:22])[F:21])=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14](Br)=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[C:29]([C:30]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40]C(C)(C)C)=[O:39])[CH2:34][CH2:33]2)=[O:31])=[CH:28][N:27]=[CH:26]1.[Li][CH2:46]CCC.CC(C)=O.[C:54](=[O:56])=[O:55].[NH4+].[Cl-]>C1COCC1>[CH2:1]([C:8]1[C:9]([C:20]([F:23])([F:22])[F:21])=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14]([C:30]([OH:31])([C:29]1[N:25]([CH3:24])[CH:26]=[N:27][CH:28]=1)[CH:32]1[CH2:37][CH2:36][N:35]([C:38](=[O:40])[CH3:46])[CH2:34][CH2:33]1)=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:54]([OH:56])([C:20]([F:23])([F:22])[F:21])=[O:55].[C:38]([OH:40])([C:20]([F:23])([F:22])[F:21])=[O:39]