HRID1486120

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID1049

Pyridine

C5H5N

HCID6367

Acetyl chloride

C2H3ClO

反应SMILES：C[C@@H]1Nc2cc(C#N)ccc2N(Cc2c(C3CC3)cnc3ccccc23)C(=O)[C@H]1NC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C

HCID118292692

未命名化合物

PRODUCTS

产物

反应SMILES：CC(=O)N1c2cc(C#N)ccc2N(Cc2c(C3CC3)cnc3ccccc23)C(=O)[C@@H](NC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C)[C@@H]1C

HCID118292668

未命名化合物

收率 36%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID962

Water

H2O

溶剂HCID6344

Dichloromethane

CH2Cl2

PROCEDURE

实验过程

To a rt solution of tert-butyl(S)-1-((3S,4S)-7-cyano-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (70 mg, 120 μmol) in CH2Cl2 (801 μl) was added pyridine (29.4 μl, 360 μmol), followed by acetyl chloride (12.8 μl, 180 μmol), dropwise. The reaction was stirred at rt for 22 h, then diluted with H2O and extracted with CH2Cl2. The combined organic layers were washed with sat. aq. NaHCO3 and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by reverse phase preparative HPLC then flash chromatography to provide tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (26.8 mg, 36%) as a white solid. MS m/z 625 (MH)+.

WORKUP

后处理

extractionextracted with CH2Cl2
washThe combined organic layers were washed with sat. aq. NaHCO3 and sat. aq. NaCl
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by reverse phase preparative HPLC

来源与证据

来源类型: Open Reaction Database
ORD记录: ord-3102dd3d405a4f5e9f60e456e02cc1c7
来源数据集: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
专利号: US09422331B2
来源说明: uspto-grants-2016_08

反应SMILES

[C:1]([C:3]1[CH:43]=[CH:42][C:6]2[N:7]([CH2:28][C:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=[CH:31][C:30]=3[CH:39]3[CH2:41][CH2:40]3)[C:8](=[O:27])[C@@H:9]([NH:13][C:14](=[O:26])[C@@H:15]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH3:16])[C@H:10]([CH3:12])[NH:11][C:5]=2[CH:4]=1)#[N:2].N1C=CC=CC=1.[C:50](Cl)(=[O:52])[CH3:51]>C(Cl)Cl.O>[C:50]([N:11]1[C@@H:10]([CH3:12])[C@H:9]([NH:13][C:14](=[O:26])[C@@H:15]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:21])[CH3:22])[CH3:16])[C:8](=[O:27])[N:7]([CH2:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]=[CH:31][C:30]=2[CH:39]2[CH2:40][CH2:41]2)[C:6]2[CH:42]=[CH:43][C:3]([C:1]#[N:2])=[CH:4][C:5]1=2)(=[O:52])[CH3:51]