HRID1627293

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID11776

Triphenylphosphine

C18H15P

HCID75555

未命名化合物

结构：COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(CCCO)cc3F)n2-c2ccc(F)cc2)ccc1Cl

HCID66741190

未命名化合物

HCID135638421

Di-tert-butyl carbonimidoylbiscarbamate

C11H21N3O4

PRODUCTS

生成物

结构：COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(CCCNC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3F)n2-c2ccc(F)cc2)ccc1Cl

HCID178489992

未命名化合物

收率 126.3%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID8028

Tetrahydrofuran

C4H8O

溶剂HCID8857

Ethyl acetate

C4H8O2

PROCEDURE

实验过程

To a solution of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)propan-1-ol (407 mg, 0.73 mmol) in anhyd THF (0.97 mL) were added PPh3 (285 mg, 1.08 mmol), 1,3-bis(tert-butoxycarbonyl)guanidine (384 mg, 1.45 mmol) and diisopropyl azodicarboxylate (DIAD) (225 μL, 1.08 mmol) sequentially. After stirring overnight, the reaction mixture was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography (80% EtOAc/hexanes) to yield tert-butyl(tert-butoxycarbonylamino)(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)propylamino)methylenecarbamate (740 mg), which was taken to the next step without further purification. MS (EI) m/z 802.50 (MH+).

WORKUP

后处理

washwashed with H2O and brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe crude material was purified by flash chromatography (80% EtOAc/hexanes)

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-f24b72e0bca640e89b7320459df22b43
来源数据集: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08785488B2
来源说明: uspto-grants-2014_07

反应 SMILES

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([CH2:32][CH2:33][CH2:34]O)=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:58]([O:62][C:63]([NH:65][C:66]([NH:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])=[NH:67])=[O:64])([CH3:61])([CH3:60])[CH3:59].N(C(OC(C)C)=O)=NC(OC(C)C)=O>CCOC(C)=O.C1COCC1>[C:58]([O:62][C:63](=[O:64])[N:65]=[C:66]([NH:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[NH:67][CH2:34][CH2:33][CH2:32][C:28]1[CH:27]=[C:26]([F:36])[C:25]([CH2:24][S:23][C:14]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:37][CH3:38])[CH:4]=3)([CH3:9])[CH3:10])=[CH:12][N:13]=2)=[C:30]([F:31])[CH:29]=1)([CH3:61])([CH3:60])[CH3:59]