Malonic Acid → 2-(3-Hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

HRID 2370419

반응식

HRID 2370419 반응식
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].[C:13]([OH:19])(=O)[CH2:14]C(O)=O.[N:20]1[CH:25]=CC=C[CH:21]=1.N1C2C(=CC=CC=2)C(=O)C1=O.OC1(CC([O-])=O)C2C(=CC=C(I)C=2)NC1=O.[NH+]1C=CC=CC=1.C(N(CC)CC)C.CN(C)C(Cl)=O>C(OCC)(=O)C>[OH:12][C:5]1([CH2:14][C:13]([N:20]([CH3:25])[CH3:21])=[O:19])[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=2)[NH:7][C:6]1=[O:11]

참가 물질

9

반응물 7

HCID 867Malonic AcidHCID 1049PyridineHCID 6598Dimethylcarbamoyl ChlorideHCID 7054IsatinHCID 8471TriethylamineHCID 886955-IodoisatinHCID 67148240pyridinium (3-hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-acetate

생성물 1

HCID 591297532-(3-Hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매2회

반응 조건

온도
80 °C

실험 절차

A 2 L flask with mechanical stirrer is charged with 5-iodo-isatin (78.1 g, 0.286 mol), malonic acid (35.7 g, 0.343 mop, and pyridine (90.4 g, 1.144 mol). The mixture is heated to 80° C. When most of the isatine has dissolved, ethyl acetate (100 mL) is added to prevent blocking of the stirrer by the precipitating pyridinium (3-hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-acetate. After 1 hour, precipitation of the latter salt starts, and when the mixture has been kept stirring for another 2 hours, a suspension of the salt in an orange solution has formed. To this is added triethyl amine (43.3 g, 0.429 mol), and the salt dissolves to give a dark solution. Then a solution of dimethyl carbamoyl chloride (40 g, 0.372 mol) in ethyl acetate (50 mL) is added dropwise during 20 minutes. A solid starts to precipitate, and the mixture is stirred for another 2 hours at 80° C. Then 4 N HCl is added (350 mL), and stirring is continued for 30 additional minutes in order to hydrolyze any excess carbamoyl chloride. The mixture is then filtered, and the filter cake is washed with 50% ethanol and the with water. After drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C. 1H-NMR (DMSO-D6, 300 MHz) δ 2.62, 2.91 (2 s, 3 each, N(CH3)2); 2.91, 3.25 (AB, 2H, |2J|=16.4 Hz, CH2); 5.97 (br s, 1H, OH); 6.59 (d, 1H, 3J=7.9 Hz, H-7); 7.46 (dd, 1H, 4J=1.5 Hz, H-6); 7.54 (d, 1H, H-4); 10.15 (br s, 1H, NH). 13C-NMR (DMSO-D6, 75 MHz) δ 35.08, 37.48 (N(CH3)2); 40.86 (CH2); 73.76 (C-3); 84.29 (C-5); 112.49 (C-7); 132.44 (C-4); 136.06 (C-9); 137.72 (C-6); 143.66 (C-8); 168.93 CONMe2); 178.47 (C-2).

후처리

  1. customprecipitation of the latter salt starts, and when the mixture
  2. additiona suspension of the salt in an orange solution
  3. customhas formed
  4. dissolutionthe salt dissolves
  5. customto give a dark solution
  6. customA solid starts to precipitate
  7. stirringthe mixture is stirred for another 2 hours at 80° C
  8. additionThen 4 N HCl is added (350 mL)
  9. stirringstirring
  10. filtrationThe mixture is then filtered
  11. washthe filter cake is washed with 50% ethanol
  12. dry with materialAfter drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C

출처 및 근거

ORD 기록
ord-b351ed6fe4d44f4f8f03db0c6920266a
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08710093B2

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