1,2-Dichloroethane → 3-(2-Acetylamino-3-methylbutyryl)-5-tert-butyl-2,3-dihydro-[1,2,4] thiadiazole-2-carboxylic acid (2-benzyloxy-5-oxo-tetrahydrofuran-3-yl)-amide

HRID 900567

反応式

HRID 900567 の反応式
C(O[C:5](=[O:21])[NH:6][CH:7]1[CH2:11][C:10](=[O:12])[O:9][CH:8]1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)C=C.CC1C2C(=CC=CC=2)C(C)=C2C=1C=CC1C2=CC=CC=1.[C:42]([NH:45][CH:46]([CH:61]([CH3:63])[CH3:62])[C:47]([CH:49]1[N:53]=[C:52]([C:54]([CH3:57])([CH3:56])[CH3:55])[S:51][N:50]1C(O)=O)=[O:48])(=[O:44])[CH3:43].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.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>[CH2:14]([O:13][CH:8]1[CH:7]([NH:6][C:5]([N:50]2[CH:49]([C:47](=[O:48])[CH:46]([NH:45][C:42](=[O:44])[CH3:43])[CH:61]([CH3:63])[CH3:62])[N:53]=[C:52]([C:54]([CH3:56])([CH3:55])[CH3:57])[S:51]2)=[O:21])[CH2:11][C:10](=[O:12])[O:9]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 60017,12-Dimethylbenz(a)anthraceneHCID 757711-HydroxybenzotriazoleHCID 186237603-(2-Acetylamino-3-methylbutyryl)-5-tert-butyl-2,3-dihydro-[1,2,4]thiadiazole-2-carboxylic acidHCID 22321532(2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester

生成物 1

HCID 865905593-(2-Acetylamino-3-methylbutyryl)-5-tert-butyl-2,3-dihydro-[1,2,4] thiadiazole-2-carboxylic acid (2-benzyloxy-5-oxo-tetrahydrofuran-3-yl)-amide収率 88%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (2-benzyloxy-5-oxo-tetrahydrofuran-3-yl)-carbamic acid allyl ester (40) (0.385 g, 1.32 mmol) in DMF (2 ml) and CH2Cl2 (2 ml) was added DMBA (0.456 g, 2.92 mmol) and Pd(PPh3)4 (0.136 g, 0.12 mmol) and the solution was stirred at room temperature for 15 min. A solution of (39) in CH2Cl2 (4.5 ml) and DMF (0.5 ml) was added, followed by HOBT (0.168 g, 1.24 mmol) and EDC (0.256 g, 1.33 mmol). The reaction was stirred at room temperature for 18 hours under N2. The solvent was evaporated. The crude material was dissolved in EtOAc and washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine and was dried over anhydrous Na2SO4, filtered and evaporated to give a yellow solid. Purification by flash column chromatography gave the title compound (41) as a mixture of diastereomers (374 mg, 88% yield) 1H-NMR (500 MHz, CDCl3) δ 0.75-1.05 (m, 6H), 1.19-1.34 (m, 9H), 1.93-2.08 (m, 3H), 2.19-2.50 (m, 2H), 2.80-3.03 (m, 1H), 4.56-4.93 (m, 3H), 5.02-5.20 (m, 1H) 5.46-5.56 (m, 1H), 5.95-6.16 (m, 2H), 6.86-6.95 (m, 1H), 7.20-7.43 (m, 5H). Analytical HPLC (C18 column), (mixture of diastereomers) 8.58 min. LC-MS (ES+) m/e=519.2 (M+H).

後処理

  1. stirringThe reaction was stirred at room temperature for 18 hours under N2
  2. customThe solvent was evaporated
  3. dissolutionThe crude material was dissolved in EtOAc
  4. washwashed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine
  5. dry with materialwas dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow solid
  9. customPurification by flash column chromatography

出典と根拠

ORDレコード
ord-ab02d64d25d04db493b809e918688cf7
出典データセット
uspto-grants-2008_04
特許番号
US07358273B2

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