1,2-Dichloroethane → 1-[2-(4-Amino-3-chloro-benzoylamino)-propionyl]-pyrrolidine-2-carboxylic acid (5-oxo-2-phenethyloxy-tetrahydro-furan-3-yl)-amide

HRID 900581

반응식

HRID 900581 반응식
C(O[C:5](=[O:22])[NH:6][CH:7]1[CH2:11][C:10](=[O:12])[O:9][CH:8]1[O:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)C=C.CC1C2C(=CC=CC=2)C(C)=C2C=1C=CC1C2=CC=CC=1.[NH2:43][C:44]1[CH:64]=[CH:63][C:47]([C:48]([NH:50][CH:51]([CH3:62])[C:52]([N:54]2[CH2:58][CH2:57][CH2:56][CH:55]2C(O)=O)=[O:53])=[O:49])=[CH:46][C:45]=1[Cl:65].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:12]=[C:10]1[O:9][CH:8]([O:13][CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:7]([NH:6][C:5]([CH:55]2[CH2:56][CH2:57][CH2:58][N:54]2[C:52](=[O:53])[CH:51]([NH:50][C:48](=[O:49])[C:47]2[CH:63]=[CH:64][C:44]([NH2:43])=[C:45]([Cl:65])[CH:46]=2)[CH3:62])=[O:22])[CH2:11]1

참가 물질

9

반응물 6

HCID 111,2-DichloroethaneHCID 60017,12-Dimethylbenz(a)anthraceneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 18465651HCID 18465651, 화합물HCID 186236851-[2-(4-Amino-3-chloro-benzoylamino)-propionyl]-pyrrolidine-2-carboxylic acid

생성물 1

HCID 229775121-[2-(4-Amino-3-chloro-benzoylamino)-propionyl]-pyrrolidine-2-carboxylic acid (5-oxo-2-phenethyloxy-tetrahydro-furan-3-yl)-amide수율 73%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (5-oxo-2-phenethyloxy-tetrahydro-furan-3-yl)-carbamic acid allyl ester (194 mg, 0.54 mmol) (prepared as described for (40) using phenethyl alcohol) in anhydrous CH2Cl2 (5 mL) at 0° C. was added DMBA (196 mg, 1.26 mmol) and Pd(PPh3)4 (32 mg, 0.03 mmol). The solution was stirred for 15 min and a solution of 97a (prepared from 96a by treatment with TFA in CH2Cl2) (166 mg, 0.49 mmol) and DIEA (680 μl, 3.90 mmol) in CH2Cl2 (2 mL) was added followed by HOBT (98 mg, 0.73 mmol) and EDC (122 mg, 0.63 mmol). The solution was stirred at 0° C. for 15 min then at room temperature for 18 hours. The solvent was removed in vacuo and the residue dissolved in EtOAc then washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine. Dried over anhydrous Na2SO4 and evaporated to give an orange solid which was purified by flash column chromatography, using CH2Cl2/MeOH (99/1 to 97/3%) to yield the title compound as a white solid (190 mg, 73% yield). 1H-NMR (500 MHz, CD3OD) δ 1.29 (d, 0.6H), 1.41 (d, 2.4H), 1.78 (m, 1H), 2.08 (m, 3H), 2.56 (m, 1H), 2.77 (dd, 1H), 2.94 (t, 2H), 3.53 (m, 0.3H), 3.67 (m, 0.8H), 3.85 (m, 2H), 3.96-4.08 (m, 1H), 4.40 (m, 2H), 4.62 (m, 1H), 4.67-4.79 (m, 1H), 5.57 (d, 0.7H), 5.60 (d, 0.3H), 6.78 (dd, 1H), 7.21 (m, 5H), 7.58 (m, 1H), 7.79 (m, 1H), 8.26 (d, 1H). Analytical HPLC 14.52 min. LC-MS (ES+) m/e=543.2 (MH+).

후처리

  1. stirringThe solution was stirred at 0° C. for 15 min
  2. waitat room temperature for 18 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue dissolved in EtOAc
  5. washthen washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine
  6. dry with materialDried over anhydrous Na2SO4
  7. customevaporated
  8. customto give an orange solid which
  9. customwas purified by flash column chromatography

출처 및 근거

ORD 기록
ord-24bca184c735459fb956918426850b88
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07358273B2

연결된 노트

불러오는 중…