Triethylamine → benzyl(3-(benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

HRID 80691노트

반응식

HRID 80691 반응식
[CH2:1]([O:8][C:9]1[C:32](=[O:33])[N:13]2[CH2:14][CH:15]3[CH2:20][CH2:19][C:18]([NH:21][C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])([C:12]2=[N:11][C:10]=1[C:34]([OH:36])=O)[CH2:17][CH2:16]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:44][CH2:45][C:46](=[O:55])[CH2:47][C:48]1[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[CH2:25]([O:24][C:22](=[O:23])[NH:21][C:18]12[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]1[C:32](=[O:33])[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:10]([C:34](=[O:36])[NH:44][CH2:45][C:46](=[O:55])[CH2:47][C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=3)[N:11]=[C:12]21)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 132906742-Propanone, 1-amino-3-(4-fluorophenyl)-, hydrochloride (1:1)HCID 679603133-(Benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid

생성물 1

HCID 71100903benzyl(3-(benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate수율 77%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid, Intermediate 4 (400 mg, 0.817 mmol) in CH2Cl2 (8 mL) was added oxalyl chloride (0.114 mL, 1.307 mmol) followed by 1 drop of DMF. After stirring for 2 h, the mixture was concentrated under reduced pressure. The crude acid chloride was then diluted with dichloromethane (5 mL)) and added to a stirred solution of 1-amino-3-(4-fluorophenyl)propan-2-one HCl (183 mg, 0.899 mmol) and triethylamine (0.456 mL, 3.27 mmol) in CH2Cl2 (8.00 mL) and the resulting solution stirred at room temperature. After 16 h the reaction mixture was poured into sat. NaHCO3 and extracted with dichloromethane (50 mL×3), dried (Na2SO4), filtered and concentrated to give a yellow oil. The crude product was then purified by silica gel chromatography (50-100% EtOAc/hexane) to afford the title compound (400 mg, 0.626 mmol, 77% yield) as a light yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.99 (1H, br. s.), 7.49 (2H, d, J=5.80 Hz), 7.28-7.37 (8H, m), 7.15 (2H, dd, J=8.55, 5.49 Hz), 7.01-7.04 (2H, m), 6.79 (1H, br. s.), 5.32 (2H, s), 5.06 (2H, s), 4.17 (2H, d, J=4.88 Hz), 4.12 (2H, d, J=3.66 Hz), 3.69 (2H, s), 2.67-2.78 (2H, m), 2.47 (1H, br. s.), 1.89-2.01 (4H, m), 1.64-1.72 (2H, m). LCMS (M+H)=640.04.

후처리

  1. concentrationthe mixture was concentrated under reduced pressure
  2. additionThe crude acid chloride was then diluted with dichloromethane (5 mL)) and
  3. stirringthe resulting solution stirred at room temperature
  4. extractionextracted with dichloromethane (50 mL×3)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil
  9. customThe crude product was then purified by silica gel chromatography (50-100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-730facc2e5cc470a999e5e1633875660
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846659B2

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