Diisopropylethylamine → Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

HRID 133810노트

반응식

HRID 133810 반응식
[C:1]12([CH:11]([NH:15][CH3:16])[C:12]([OH:14])=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:50]/[C:51](=[CH:57]\[C@@H:58]([N:62]([CH3:71])[C:63](=[O:70])[C@H:64]([C:66]([CH3:69])([CH3:68])[CH3:67])[NH2:65])[CH:59]([CH3:61])[CH3:60])/[C:52]([O:54][CH2:55][CH3:56])=[O:53].C(N(C(C)C)CC)(C)C>ClCCl>[C:1]12([C@@H:11]([NH:15][CH3:16])[C:12]([NH:65][C@H:64]([C:63]([N:62]([CH3:71])[C@@H:58]([CH:59]([CH3:61])[CH3:60])/[CH:57]=[C:51](\[CH3:50])/[C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:70])[C:66]([CH3:69])([CH3:68])[CH3:67])=[O:14])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 11229817Adamantan-1-yl-methylamino-acetic acid

생성물 1

HCID 86596600Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To adamantan-1-yl-methylamino-acetic acid (0.447 g, 2.0 mmol, from Reference Example 6) in dichloromethane (17 mL) is added PyBOP (1.04 g, 2.0 mmol). After 15 min ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.625 g, 2.0 mmol, WO 99/32509) in dichlormethane (5 mL) is added, followed by diisopropylethylamine (0.75 mL, 4.3 mmol). This is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo and the residue treated with ethyl acetate and water. The ethyl acetate layer is dried over sodium sulfate and purified by hplc. The two diastereomers are partially separated. The first isomer is assigned the SSS configuration and contained 33.4% of the RSS isomer. MS: m/z 518.3 (M+1). The second isomer is assigned the RSS configuration and contained 8.9% of the SSS isomer. MS: m/z 518.3 (M+1).

후처리

  1. customThe reaction mixture is evaporated in vacuo
  2. additionthe residue treated with ethyl acetate and water
  3. dry with materialThe ethyl acetate layer is dried over sodium sulfate
  4. custompurified by hplc
  5. customThe two diastereomers are partially separated

출처 및 근거

ORD 기록
ord-a48711c029d742829bfac315dffebdea
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07390910B2

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