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 1861246

Reaction equation

HRID 1861246 reaction equation
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

Participants

9

Reactant 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

Product 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)-amideYield 88%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e43d6d2d0d034089afd0764b85ff0f36
Source dataset
uspto-grants-2003_03
Patent number
US06531474B1

Linked notes

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