HRID51540

反应详情

EQUATION

反应方程式

REACTANTS

反应物

$结构：O=C(O)/C=C\C(=O)O$

HCID444266

Maleic acid

C4H4O4

结构：Cc1cc(Oc2ccccc2)ccc1-c1cn([C@H]2CC[C@H](N3CCN(C)CC3)CC2)c2ncnc(N)c12

HCID178428809

未命名化合物

PRODUCTS

生成物

$结构：Cc1cc(Oc2ccccc2)ccc1-c1cn([C@H]2CC[C@H](N3CCN(C)CC3)CC2)c2ncnc(N)c12.O=C(O)/C=C\C(=O)O.O=C(O)/C=C\C(=O)O.O=C(O)/C=C\C(=O)O$

HCID178428810

未命名化合物

收率 23.9%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID702

Ethanol

C2H6O

2 次

PROCEDURE

实验过程

A mixture of trans-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.347 g, 0.000788 mol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl phenyl ether (0.27 g, 0.000867 mol), tetrakis(triphenyl-phosphine)palladium(0) (0.054 g, 0.000047 mmol), and sodium carbonate (0.209 g, 0.00197 mol) in N,N-dimethylformamide (15 mL) and water (10 mL) was heated at 80° C. under an atmosphere of nitrogen for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent removed under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The water phase was further extracted with ethyl acetate and the combined organic extracts were dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel using triethylamine/dichloromethane (5:95) followed by methanol/triethylamine/ dichloromethane (3:5:92) as mobile phase to yield trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.376 g, 0.000757 mol). Trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)-cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.376 g, 0.000757 mol) was dissolved in refluxing ethanol (10 mL) and a preheated solution of maleic acid (0.264 g, 0.00227 mol) in ethanol (5 mL) was added. The mixture was refluxed for 15 minutes, cooled to ambient temperature and the precipitate collected by filtration, washed with cool ethanol and dried to give trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)-cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate (0.153 g, 0.000181 mol): 1H NMR (DMSO-d6, 400 MHz) 8.22 (s, 1H), 7.42 (m, 3H), 7.25 (d, 1H), 7.17 (t, 1H), 7.09 (d, 2H), 7.02 (s, 1H), 6.89 (d, 1H), 6.16 (s, 6H), 4.58 (m, 1H), 3.3 (br, 9H), 2.68 (s, 3H), 2.22 (s, 3H), 2.01 (br, 6H), 1.57 (br, 2H) RP-HPLC (Hypersil C18, 5 μm, 250×4.6 mm; 25%-100% over 23 min with 0.1 M ammonium acetate, 1 mL/min) Rt 7.30 min. MS: MH+497.

WORKUP

后处理

temperatureThe mixture was refluxed for 15 minutes
filtrationthe precipitate collected by filtration
washwashed with cool ethanol
customdried

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-75959aa625d14d18ace2943d3b9a0abd
来源数据集: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
专利: US06713474B2
来源说明: uspto-grants-2004_03

反应 SMILES

[CH3:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:22]([NH2:24])=[N:21][CH:20]=[N:19][C:18]=2[N:17]([C@H:25]2[CH2:30][CH2:29][C@H:28]([N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)[CH2:27][CH2:26]2)[CH:16]=1.[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42]>C(O)C>[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42].[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42].[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42].[CH3:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:22]([NH2:24])=[N:21][CH:20]=[N:19][C:18]=2[N:17]([C@H:25]2[CH2:26][CH2:27][C@H:28]([N:31]3[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]3)[CH2:29][CH2:30]2)[CH:16]=1