Dicyclohexylcarbodiimide → Boc-norvaline leucinamide

HRID 399100

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HRID 399100 반응식
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH2:10][CH2:11][CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C@H:17]([C:22]([NH2:24])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH2:10][CH2:11][CH3:12])([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2].[NH2:16][C@H:17]([C:22]([NH2:24])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20]

참가 물질

6

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 69640LeucinamideHCID 757711-HydroxybenzotriazoleHCID 2733748(2S)-2-(((tert-butoxy)carbonyl)amino)pentanoic acid

생성물 1

HCID 18665783Boc-norvaline leucinamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

Boc-norvaline (2.0 g, 9.2 mmol) and leucinamide (1.53 g, 9.2 mmol) were dissolved in dry DMF (90 mL). The reaction was cooled to 0° C. and DCC (2.3 g, 11 mmol), HOBt (1.48 g, 11 mmol), and DEA (1.9 mL, 11 mmol) added. The mixture was stirred for 20 min at 0° C. and allowed to slowly warm to room temperature overnight (17 h). The mixture was concentrated to 1/3 its original volume, cooled, and filtered. The filtrate was concentrated, affording a yellow oil which was purified by column chromatography (SiO2, 1:1 hexanes/EtOAc→EtOAc) providing Boc-norvaline-leucinamide as white solid (selected signals 400 MHz, 1H NMR, CDCI3: δ 4.93 (m, 1 H), 4.45 (m, 1 H), 3.99 (m, 1 H), 1.81-1.71 (m, 2 H), 1.68-1.50 (m, 4 H), 1.41 (s, 9 H), 1.4-1.3 (m, 2 H), 0.9 (m, 9 H)). The Boc-protecting group was removed by treatment of Boc-norvaline-leucinamide (1.5 g, 4.6 mmol) with 50% TFA/DCM (60 mL) at room temperature (30 min). The reaction mixture was concentrated in vacuo and the peptide triturated with diethyl ether and dried in vacuo overnight providing norvaline-leucinamide as a foamy white solid (Electrospray MS M+H=230.1). Boc-valine (233 mg, 1.1 mmol) and norvaline-leucinamide (246 mg, 1.1 mmol) were dissolved in DMF (5 mL) and the solution cooled to 0° C. DCC (266 mg, 1.3 mmol), HOBt (174 mg, 1.3 mmol), and DIEA (224 μL, 1.3 mmol) were added and the reaction allowed to slowly warm to RT (overnight, 17 h). The reaction was filtered and the filtrate concentrated in vacuo affording a solid which was purified by column chromatography (SiO2, EtOAc). This provided the desired Boc-valine-norvaline-leucinamide as a white solid.

후처리

  1. temperatureto slowly warm to room temperature overnight (17 h)
  2. concentrationThe mixture was concentrated to 1/3 its original volume
  3. temperaturecooled
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customaffording a yellow oil which
  7. customwas purified by column chromatography (SiO2, 1:1 hexanes/EtOAc→EtOAc)

출처 및 근거

ORD 기록
ord-00d3529f05684f1b8fa9fc2ca0b5d22b
출처 데이터셋
uspto-grants-1998_10
특허 번호
US05817757

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