Triethylamine → {3-methoxy-[1,2,4]-thiadiazol-5-yl}carbamoyl-L-leucine L-proline methyl ester

HRID 1275606노트

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HRID 1275606 반응식
[NH2:1][C:2]1[S:6][N:5]=[C:4]([O:7][CH3:8])[N:3]=1.[C:9](N1C=CN=C1)(N1C=CN=C1)=[O:10].C(N(CC)CC)C.[NH2:28][C@H:29]([C:34]([OH:36])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32].Cl.[CH3:38][O:39][C:40](=[O:46])[C@@H:41]1[CH2:45][CH2:44][CH2:43][NH:42]1>ClCCl.CN(C=O)C>[CH3:8][O:7][C:4]1[N:3]=[C:2]([NH:1][C:9]([NH:28][C@H:29]([C:34]([OH:36])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:10])[S:6][N:5]=1.[CH3:38][O:39][C:40](=[O:46])[C@@H:41]1[CH2:45][CH2:44][CH2:43][NH:42]1

참가 물질

7

반응물 4

HCID 8471Triethylamine2회HCID 682631,1'-CarbonyldiimidazoleHCID 3141795-Amino-3-methoxy-1,2,4-thiadiazoleHCID 86756120L-leucine L-proline methyl ester hydrochloride

생성물 1

HCID 70080342{3-methoxy-[1,2,4]-thiadiazol-5-yl}carbamoyl-L-leucine L-proline methyl ester수율 76.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
120 °C

실험 절차

To 5-amino-3-methoxy-[1,2,4]thiadiazole (1.31 g, 10 mmol) in dichloromethane (15 mL) at room temperature was added 1,1'-carbonyldiimidazole, CDl, (1.78 g,11 mmol) followed by triethylamine (2.1 mL, 15 mmol). The resulting suspension was stirred under nitrogen for 2.5 h. Volatile materials were removed in vacuo and the residue was dissolved in DMF (20 mL). The latter was then added to a solution of L-leucine-L-proline methyl ester hydrochloride (4.18 g,15 mmol) and triethyl amine (2.1 mL, 15.1 mmol) in DMF (25 mL). The resulting mixture was heated at 120° C. for 2 h and then allowed to cool to room temperature. Volatile materials were removed in vacuo and the residue was diluted with ethyl acetate (250 mL) and water (100 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers was dried (sodium sulfate), filtered and concentrated in vacuo. Purification by column chromatography on silica gel using a solvent mixture of hexane and ethyl acetate (1/1 and 2/3) afforded {3-methoxy-[1,2,4]-thiadiazol-5-yl}carbamoyl-L-leucine-L-proline methyl ester as a light yellow foam (3.2 g, 76.6%). M.p. 88-90° C.; 1H-NMR (CDCl3) δ12.75 (s, 1H, NH), 6.70 (d, J=12.0 Hz, 1H, NH), 4.79-4.87 (m, 1H, NCHpro), 4.54-4.59 (dd, J=11.8, 6.0 Hz, 1H, NCH), 4.12 (s, 3H, OMe), 3.64-3.90 (m, 2H, NCH2 pro), 1.56-2.26 (m, 6H, 3CH2), 0.94-1.12 (two d, J=9.7 Hz, 7H, 2CH3 +CH); 13C-NMR (CDCl3) δ178.3 (C3), 172.3, 171.1 (CO2), 165.9 (C5), 153.7 (NHC=ONH), 58.8, 56.6, 52.2, 49.8, 47.0 (CH2), 42.0 (CH2), 29.0 (CH2), 24.8 (CH2), 24.5, 23.2, 22.0; MS (m/z) 400 (M+ +1),326, 271, 243, 209,158, 130, 87.

후처리

  1. customVolatile materials were removed in vacuo
  2. dissolutionthe residue was dissolved in DMF (20 mL)
  3. temperatureto cool to room temperature
  4. customVolatile materials were removed in vacuo
  5. additionthe residue was diluted with ethyl acetate (250 mL) and water (100 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  7. dry with materialThe combined organic layers was dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography on silica gel using
  11. additiona solvent mixture of hexane and ethyl acetate (1/1 and 2/3)

출처 및 근거

ORD 기록
ord-69cb800bab8d445195c9bc5c85fdd8ca
출처 데이터셋
uspto-grants-2000_12
특허 번호
US06162791

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