Dimethyl Sulfoxide → (r)-6-Methyl-4'-trifluoromethylbiphenyl-2-carboxylic acid (2-methoxycarbonylaminoindan-5-yl)-amide

HRID 1531289노트

반응식

HRID 1531289 반응식
[CH3:1][O:2][C:3](=[O:15])[NH:4][C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH2:14])[CH:11]=2)[CH2:6]1.CS(C)=O.N1C=CC=CC=1.[CH3:26][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]([C:43](Cl)=[O:44])[C:32]=1[C:33]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=1>C(Cl)Cl>[CH3:1][O:2][C:3]([NH:4][C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH:14][C:43]([C:31]3[C:32]([C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:40])([F:42])[F:41])=[CH:35][CH:34]=4)=[C:27]([CH3:26])[CH:28]=[CH:29][CH:30]=3)=[O:44])[CH:11]=2)[CH2:6]1)=[O:15]

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 1049PyridineHCID 110556396-Methyl-4'-trifluoromethylbiphenyl-2-carboxylic acid chlorideHCID 11413084(R)-Methyl (5-amino-2,3-dihydro-1H-inden-2-yl)carbamate

생성물 1

HCID 9869236(r)-6-Methyl-4'-trifluoromethylbiphenyl-2-carboxylic acid (2-methoxycarbonylaminoindan-5-yl)-amide

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To an ice bath cooled solution of (R)-(5-aminoindan-2-yl)-carbamic acid methyl ester (9.5 g, 46.1 mmol) prepared as described in example 12 ([α]D=−26.29 (c=9.87 mg/mL, DMSO); mp 144-145° C.) and pyridine (4.48 mL, 55.5 mmol) in 200 mL of methylene chloride is added 6-methyl-4′-trifluoromethyl-biphenyl-2-carboxylic acid chloride (80.5 mL of a 0.63 M solution in methylene chloride, 50.7 mmol). The reaction is stirred for 15 minutes at room temperature. The mixture is washed with 1N HCl, bicarbonate and brine. The organic layer is dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The product is purified by crystallization from ethyl acetate/hexanes (1:2) to give (R)-6-methyl-4′-trifluoromethylbiphenyl-2-carboxylic acid (2-methoxycarbonylaminoindan-5-yl)-amide (the compound of example 13(i)) as a crystalline solid, mp 112-114° C. MS (ES+), m/z469 (M+1); [α]D=−12.85° (c=11.36 mg/ml DMSO).

후처리

  1. customprepared
  2. washThe mixture is washed with 1N HCl, bicarbonate and brine
  3. dry with materialThe organic layer is dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe product is purified by crystallization from ethyl acetate/hexanes (1:2)

출처 및 근거

ORD 기록
ord-8ca476066c754413ba74d577d5126846
출처 데이터셋
uspto-grants-2001_03
특허 번호
US06197798B1

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