HRID1529389

反应详情

EQUATION

反应方程式

REACTANTS

反应物

结构：O[C@@H]1CN(c2cncc(-c3nn(C4CCCCO4)c4ccc(-c5c(F)cccc5F)cc34)n2)CC[C@@H]1O

HCID67959584

未命名化合物

PRODUCTS

生成物

结构：OC1CCN(c2cncc(-c3nn(C4CCCCO4)c4ccc(-c5c(F)cccc5F)cc34)n2)CC1O.O[C@@H]1CN(c2cncc(-c3n[nH]c4ccc(-c5c(F)cccc5F)cc34)n2)CC[C@@H]1O

HCID88532872

未命名化合物

收率 29%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID313

Hydrochloric Acid

ClH

溶剂HCID3776

Isopropanol

C3H8O

CONDITIONS

反应条件

温度: 70 °C

PROCEDURE

实验过程

A slurry of racemic cis-1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol (0.100 g, 0.197 mmol) in 3 mL 5-6 N HCl in IPA (acros organics) was sealed and the slurry was heated to 70° C. After 1.5 h, the reaction was cooled and concentrated in vacuo. This material was dissolved in DMSO and purified by shimadzu RPHPLC, 15-70% ACN/H2O with 0.1% TFA; product-containing fractions were concentrated in vacuo. The material was partitioned between sat'd aq NaHCO3 and DCM, and the aq. layer was extracted 3×10% MeOH/DCM. The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give the title compound (0.024 g, 29% yield) as an off-white solid: MS (ESI, pos. ion) m/z: 424 (M+1).

WORKUP

后处理

temperaturethe reaction was cooled
concentrationconcentrated in vacuo
dissolutionThis material was dissolved in DMSO
custompurified
concentrationproduct-containing fractions were concentrated in vacuo
customThe material was partitioned between sat'd aq NaHCO3 and DCM
extractionthe aq. layer was extracted 3×10% MeOH/DCM
dry with materialThe combined organics were dried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-cff816d5e5d04f8d8bba0dc44c93f36d
来源数据集: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
专利: US09090593B2
来源说明: uspto-grants-2015_07

反应 SMILES

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C@H:33]([OH:36])[C@H:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1>Cl.CC(O)C>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C@H:33]([OH:36])[C@H:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1.[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][CH:33]([OH:36])[CH:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1