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

反応式

HRID 900581 の反応式
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

参加物

9

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6344Dichloromethane溶媒2 回

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-24bca184c735459fb956918426850b88
出典データセット
uspto-grants-2008_04
特許番号
US07358273B2

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