Lithium Hydroxide → 1-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide

HRID 1865719노트

반응식

HRID 1865719 반응식
O.[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([OH:7])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:53]/[C:54](=[CH:60]\[C@@H:61]([N:65]([CH3:74])[C:66](=[O:73])[C@H:67]([C:69]([CH3:72])([CH3:71])[CH3:70])[NH2:68])[CH:62]([CH3:64])[CH3:63])/[C:55]([O:57]CC)=[O:56].[OH-].[Li+]>ClCCl.CO.ClCCl.O.O1CCCC1.O>[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([NH:68][C@H:67]([C:66]([N:65]([C@@H:61]([CH:62]([CH3:64])[CH3:63])/[CH:60]=[C:54](/[C:55]([OH:57])=[O:56])\[CH3:53])[CH3:74])=[O:73])[C:69]([CH3:71])([CH3:72])[CH3:70])=[O:7]

참가 물질

11

반응물 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 162119581-Methyl-L-proline--water (1/1)

생성물 1

HCID 115963751-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide수율 28%

시약·촉매·용매 5

HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매2회HCID 8028Tetrahydrofuran용매HCID 21908982Water methylene chloride용매

실험 절차

To a solution of N-methyl-L-proline monohydrate (0.26 g, 1.79 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.4 g, 2.69 mmol) in anhydrous dichloromethane (3.0 ml) at 25° C. is added diisopropylethylamine (0.63 ml, 3.62 mmol) under an inert atmosphere. To this solution is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.39 g, 1.27 mmol, WO 99/32509) in anhydrous dichloromethane (2.0 ml). The resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo. The residue (300 mg, 0.78 mmol) is dissolved in methanol (6.85 ml), water (1.8 ml) and tetrahydrofuran (3.25 ml). To this reaction mixture is added aqueous lithium hydroxide solution (3.54 ml, 3.54 mol) The resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with citric acid, brine, dried over sodium sulfate and filtered. The solvent is removed in vacuo, and the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a yellow oil, 0.08 g (28% yield). MS: m/z 396.28 (M+1)

후처리

  1. customThe resulting reaction mixture
  2. customThe reaction mixture is evaporated in vacuo
  3. stirringis stirred at room temperature overnight
  4. washThe organic layer is washed with citric acid, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent is removed in vacuo
  8. customthe residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

출처 및 근거

ORD 기록
ord-d3dcd8dbf5dc4e9887bcbea06143be5d
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07626023B2

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