HRID564622

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID6422

未命名化合物

HCID10340

Carbonic acid sodium salt (1:2)

CNa2O3

结构：C[C@H]1CN(Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CCN1C(=O)OC(C)(C)C

HCID57813257

未命名化合物

结构：CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2cc(Br)ccc2OC)c1

HCID57813267

未命名化合物

PRODUCTS

生成物

结构：CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2cc(-c3cccc(CN4CCN[C@@H](C)C4)c3)ccc2OC)c1

HCID57813414

未命名化合物

收率 14.4%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID962

Water

H2O

溶剂HCID6344

Dichloromethane

CH2Cl2

溶剂HCID31275

1,4-Dioxane

C4H8O2

PROCEDURE

实验过程

N-{[5-Bromo-2-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (97 mg, 0.00015 mol) in dioxane (4 mL) and 1,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate (81.2 mg, 0.000195 mol) were treated with Na2CO3 (48 mg, 0.00045 mol) and 0.75 mL H2O. The mixture was degassed for 15 min with N2, and then treated with tetrakistriphenylphosphine palladium (0) (17.3 mg, 0.000015 mol). The reaction was microwaved at 150° C. for 30 min. The reaction was quenched with H2O, then diluted and extracted with EtOAc (2×). Combined organic extracts were washed with H2O, sat. aq. NaCl and dried (Na2SO4) and concentrated to give 206.6 mg crude t-BOC product. The crude product was taken up in DCM (10 mL) containing 25% TFA and allowed to stand at room temperature for 3 h. LC-MS showed the reaction to be complete. Solvent was stripped off. Purification was carried out on Gilson HPLC instrument with acetonitrile-water (0.1% TFA) gradient; C18-RP column. Fractions containing the clean desired product were combined; diluted with EtOAc; washed with sat. aq. NaHCO3; and the aq. phase was back-extracted with EtOAc. Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. It was taken up in a small amount of DCM and transferred to a vial and pumped down to afford the title compound as a beige colored solid (16.4 mg, 14%). LC-MS m/z 759.4 (M+H)+.

WORKUP

后处理

customThe mixture was degassed for 15 min with N2
customThe reaction was microwaved at 150° C. for 30 min
customThe reaction was quenched with H2O
additiondiluted
extractionextracted with EtOAc (2×)
washCombined organic extracts were washed with H2O, sat. aq. NaCl
dry with materialdried (Na2SO4)
concentrationconcentrated
customto give 206.6 mg crude t-BOC product
customthe reaction
customPurification
additionFractions containing the clean desired product
additiondiluted with EtOAc
washwashed with sat. aq. NaHCO3
extractionand the aq. phase was back-extracted with EtOAc
washCombined organic extracts were washed with sat. aq. NaCl
dry with materialdried (Na2SO4)
concentrationconcentrated to a residue

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-45d62c8b6a34406aa6f50b8c0d00c8a1
来源数据集: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08067408B2
来源说明: uspto-grants-2011_11

反应 SMILES

Br[C:2]1[CH:3]=[CH:4][C:5]([O:42][CH3:43])=[C:6]([CH2:8][NH:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([NH:20][CH2:21][C:22]3[C:23]([NH:35][CH:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[C:24]4[CH:32]=[N:31][N:30]([CH2:33][CH3:34])[C:25]4=[N:26][C:27]=3[CH2:28][CH3:29])=[O:19])[CH:13]=2)=[O:11])[CH:7]=1.[CH3:44][C@H:45]1[CH2:50][N:49]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54](B3OC(C)(C)C(C)(C)O3)[CH:53]=2)[CH2:48][CH2:47][N:46]1C(OC(C)(C)C)=O.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O>O1CCOCC1.C(Cl)Cl.O>[CH2:33]([N:30]1[C:25]2=[N:26][C:27]([CH2:28][CH3:29])=[C:22]([CH2:21][NH:20][C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([C:10]([NH:9][CH2:8][C:6]4[CH:7]=[C:2]([C:54]5[CH:55]=[CH:56][CH:57]=[C:52]([CH2:51][N:49]6[CH2:48][CH2:47][NH:46][C@@H:45]([CH3:44])[CH2:50]6)[CH:53]=5)[CH:3]=[CH:4][C:5]=4[O:42][CH3:43])=[O:11])[CH:13]=3)=[O:19])[C:23]([NH:35][CH:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[C:24]2[CH:32]=[N:31]1)[CH3:34]