Dimethylamine → Boc-Lys(Z)-Lys(Boc)-Lys(Boc)-Lys(Z)-OMe

HRID 592507노트

반응식

HRID 592507 반응식
[NH:1](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:2]([C:15]([NH:17][C@H:18]([C:31]([NH:33][C@H:34]([C:50]([O:52][CH3:53])=[O:51])[CH2:35][CH2:36][CH2:37][CH2:38][NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])=[O:32])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].CNC.[NH:74]([C:94]([O:96][C:97]([CH3:100])([CH3:99])[CH3:98])=[O:95])[C@H:75]([C:91](O)=[O:92])[CH2:76][CH2:77][CH2:78][CH2:79][NH:80][C:81]([O:83][CH2:84][C:85]1[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=1)=[O:82].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C1COCC1.C(Cl)(Cl)Cl.CO>[NH:74]([C:94]([O:96][C:97]([CH3:100])([CH3:99])[CH3:98])=[O:95])[C@H:75]([C:91]([NH:1][C@H:2]([C:15]([NH:17][C@H:18]([C:31]([NH:33][C@H:34]([C:50]([O:52][CH3:53])=[O:51])[CH2:35][CH2:36][CH2:37][CH2:38][NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])=[O:32])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])=[O:92])[CH2:76][CH2:77][CH2:78][CH2:79][NH:80][C:81]([O:83][CH2:84][C:85]1[CH:86]=[CH:87][CH:88]=[CH:89][CH:90]=1)=[O:82]

참가 물질

9

반응물 5

HCID 674DimethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724765Boc-Lys(Z)-OHHCID 131734555Fmoc-Lys(Boc)-Lys(Boc)-Lys(Z)-OMe

생성물 1

HCID 131734554Boc-Lys(Z)-Lys(Boc)-Lys(Boc)-Lys(Z)-OMe수율 59.1%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6212Chloroform용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 14 (1.48 g, 1.52 mmol) in THF (30 mL), was added dimethyl amine (15.2 mL, 2M in THF, 30.4 mmol) at 0° C. This reaction was allowed to reach room temperature and stirred for 2 h. At this time, the reaction mixture was concentrated in vacuo. To the yellowish solid was added DCM (30 mL) and DMF (5 mL). To this solution, was added Boc-Lys(Z)—OH (0.608 g, 1.60 mmol), then HOBt (0.216 g, 1.60 mmol), then EDC.HCl (0.3063 g, 1.60 mmol). This solution was allowed to stir for 8 h at which time the organic solution was washed with 1N HCl (3×15 mL), then saturated NaHCO3 (3×15 mL), and finally H2O (3×15 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to yield a white solid. Column chromatography (2% MeOH, CHCl3) afforded the product 15 (1.0 g, 59% yield): 1H NMR (500 MHz, CDCl3) δ 8.15 (br s, 1H), 8.03 (br s, 1H), 7.88 (br s, 1H), 7.45-7.28 (m, 10H), 7.12 (br s, 1H), 6.65 (br s, 1H), 5.08 (s, 1H), 4.45-4.35 (m, 3H), 4.05 (br s, 1H), 3.67 (s, 3H), 3.11 (br s, 1H), 3.01 (br s, 1H), 1.90-1.60 (m, 8H), 1.60-1.38 (m, 44); 13C NMR (125 MHz, CDCl3) δ 173.3, 173.2, 172.7, 172.3, 157.2, 156.6, 138.4, 129.0, 128.4, 79.0, 78.1, 66.0, 55.7, 53.8, 53.4, 53.0, 52.2, 41.1, 40.9, 40.8, 32.7, 32.5, 31.6, 29.8, 29.6, 28.6, 23.7, 23.5; ESMS (FAB) m/z calcd for C66H88N8O15 (M+H)+ 1113.65, found 1113.52.

후처리

  1. customto reach room temperature
  2. concentrationAt this time, the reaction mixture was concentrated in vacuo
  3. additionTo the yellowish solid was added DCM (30 mL) and DMF (5 mL)
  4. stirringto stir for 8 h at which time the organic solution
  5. washwas washed with 1N HCl (3×15 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto yield a white solid

출처 및 근거

ORD 기록
ord-be20f15ff4434dd3baf95d5d89f6b307
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238697B2

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