Triethylamine → (S,S)-5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 384500노트

반응식

HRID 384500 반응식
Cl[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][NH:29]2)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)CC)C>CC#N>[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][N:29]2[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 67207884HCID 67207884, 화합물

생성물 1

HCID 67206277(S,S)-5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester수율 71.1%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred solution of 2-(4-chloromethyl-phenoxy)-benzothiazole (15.3 g, 55.3 mmol) and (S,S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (13.2 g, 66.4 mmol) in CH3CN (200 mL) was added triethylamine (Et3N) (11.5 mL, 82.9 mmol). The resulting solution was stirred at rt for 24 h and then concentrated. The crude residue was then partitioned between CH2Cl2 (800 mL) and saturated (satd.) aqueous (aq.) NaHCO3 (200 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (10% to 40% ethyl acetate (EtOAc) in hexanes) afforded the title compound as a white foam (17.2 g, 71%). MS (ESI): mass calcd. for C24H27N3O3S, 437.18; m/z found, 438.2 [M+H]+. 1H NMR (500 MHz, CDCl3, mixture of rotamers): 7.73 (d, J=7.1 Hz, 1H), 7.66 (d, J=7.1 Hz, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.38 (m, 1H), 7.32-7.24 (br m, 3H), 4.40 (br m, 0.5H), 4.26 (br m, 0.5H), 3.76 (br d, J=9.7 Hz, 2H), 3.63 (br d, J=10.5 Hz, 0.5H), 3.50 (br m, 1H), 3.46 (m, 0.5H), 3.18 (br m, 1H), 2.93 (br d, J=8.8 Hz, 0.5H), 2.88 (br d, J=9.4 Hz, 0.5H), 2.73 (br d, J=9.2 Hz, 0.5H), 2.55 (br d, J=9.2 Hz, 0.5H), 1.87 (br t, J=8.8 Hz, 1H), 1.74 (br d, J=9.3 Hz, 0.5H), 1.68 (br d, J=9.3 Hz, 0.5H), 1.47 (s, 9H).

후처리

  1. concentrationconcentrated
  2. customThe crude residue was then partitioned between CH2Cl2 (800 mL) and saturated (satd.) aqueous (aq.) NaHCO3 (200 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel flash chromatography (10% to 40% ethyl acetate (EtOAc) in hexanes)

출처 및 근거

ORD 기록
ord-17798335bf3747458c8fa489fcdf1980
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367719B2

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