Tetrahydrofuran → Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxobutanoate

HRID 1056203노트

반응식

HRID 1056203 반응식
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:25][C:26]([C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[N:30]=[C:31]([NH:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C:32]([CH3:38])=[N:33]2)=[O:27].C1COCC1>[NH4+].[Cl-].CCO>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10](=[O:17])[CH:11]([CH2:25][C:26]([C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[N:30]=[C:31]([NH:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C:32]([CH3:38])=[N:33]2)=[O:27])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 111285644-((tert-Butoxycarbonyl)amino)-3-oxobutanoic acid ethyl esterHCID 897821422-Bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone

생성물 1

HCID 89782058Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxobutanoate

시약·촉매·용매 2

HCID 702Ethanol용매HCID 25517Ammonium Chloride용매

실험 절차

To a 25-mL round-bottomed flask was added ethyl 4-((tert-butoxycarbonyl)amino)-3-oxobutanoate (601) (0.47 g, 1.91 mmol), K2CO3 (0.41 g, 2.97 mmol), 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (0.40 g, 1.19 mmol), THF (3 mL), and EtOH (3 mL). The reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with sat NH4Cl (5 mL) and extracted with EtOAc (10 mL). The organic extract was washed with water (5 mL), dried over Na2SO4 and concentrated. Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxobutanoate (334a) was obtained as a light yellow oil and used without further purification. m/z (ESI, +ve) 501.3 (M+H)+. To a 15-mL glass tube was added ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxobutanoate (334a), crude from previous step, NH4OAc (0.36 g, 4.71 mmol), EtOH (2 mL), and AcOH (1 mL). The tube was sealed and heated at 50° C. for 3 h. The reaction mixture was cooled to RT and was concentrated to half of its volume. The mixture was diluted with EtOAc (10 mL) and water (5 mL). The organic extract was washed with NaOH (1N, 5 mL), water (5 mL), brine (5 mL), dried over Na2SO4, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (24 g), eluting with a gradient of 0% to 30% EtOAc in hexanes to give ethyl 2-(((tert-butoxycarbonyl)amino)methyl)-5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (334b) (0.33 g, 59% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.64 (br. s., 1H), 7.82 (dd, J=1.17, 7.43 Hz, 1H), 7.58-7.64 (m, 1H), 7.41 (d, J=2.74 Hz, 1H), 7.35 (s, 1H), 6.94 (br. s., 1H), 4.53 (d, J=5.28 Hz, 2H), 4.21 (q, J=7.04 Hz, 2H), 2.56 (s, 3H), 1.58 (s, 9H), 1.39 (s, 9H), 1.30 (t, J=7.10 Hz, 3H). m/z (ESI, +ve) 482.2 (M+H)+.

후처리

  1. extractionextracted with EtOAc (10 mL)
  2. extractionThe organic extract
  3. washwas washed with water (5 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-1dbe07fe666441acb037dcd185386cae
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

반응 노트

불러오는 중…