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1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-[[(E)-3-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-[4-(4-methylpiperazin-1-yl)phenyl]-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enyl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate

HRID 1057080
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HRID 1057080 반응식
Cl.C(N=C=NCCCN(C)C)C.[NH2:13][CH2:14]/[CH:15]=[CH:16]/[C:17]1[CH2:18][C@H:19]2[C:25](=[O:26])[N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:23]3[CH:35]=[C:36]([O:41][CH2:42][CH2:43][CH2:44][O:45][C:46]4[C:47]([O:83][CH3:84])=[CH:48][C:49]5[C:55](=[O:56])[N:54]6[CH:57]=[C:58]([C:60]7[CH:65]=[CH:64][C:63]([N:66]8[CH2:71][CH2:70][N:69]([CH3:72])[CH2:68][CH2:67]8)=[CH:62][CH:61]=7)[CH2:59][C@H:53]6[C:52](=[O:73])[N:51]([CH2:74][O:75][CH2:76][CH2:77][Si:78]([CH3:81])([CH3:80])[CH3:79])[C:50]=5[CH:82]=4)[C:37]([O:39][CH3:40])=[CH:38][C:22]=3[C:21](=[O:85])[N:20]2[CH:86]=1.[CH:87]1[C:99]2[CH:98]([CH2:100][O:101][C:102]([NH:104][C@@H:105]([CH:114]([CH3:116])[CH3:115])[C:106]([NH:108][C@@H:109]([CH3:113])[C:110](O)=[O:111])=[O:107])=[O:103])[C:97]3[C:92](=[CH:93][CH:94]=[CH:95][CH:96]=3)[C:91]=2[CH:90]=[CH:89][CH:88]=1>ClCCl>[CH3:40][O:39][C:37]1[C:36]([O:41][CH2:42][CH2:43][CH2:44][O:45][C:46]2[C:47]([O:83][CH3:84])=[CH:48][C:49]3[C:55](=[O:56])[N:54]4[CH:57]=[C:58]([C:60]5[CH:61]=[CH:62][C:63]([N:66]6[CH2:71][CH2:70][N:69]([CH3:72])[CH2:68][CH2:67]6)=[CH:64][CH:65]=5)[CH2:59][C@H:53]4[C:52](=[O:73])[N:51]([CH2:74][O:75][CH2:76][CH2:77][Si:78]([CH3:80])([CH3:79])[CH3:81])[C:50]=3[CH:82]=2)=[CH:35][C:23]2[N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:25](=[O:26])[C@@H:19]3[CH2:18][C:17](/[CH:16]=[CH:15]/[CH2:14][NH:13][C:110](=[O:111])[C@@H:109]([NH:108][C:106](=[O:107])[C@@H:105]([NH:104][C:102](=[O:103])[O:101][CH2:100][CH:98]4[C:99]5[CH:87]=[CH:88][CH:89]=[CH:90][C:91]=5[C:92]5[C:97]4=[CH:96][CH:95]=[CH:94][CH:93]=5)[CH:114]([CH3:116])[CH3:115])[CH3:113])=[CH:86][N:20]3[C:21](=[O:85])[C:22]=2[CH:38]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11165770Fmoc-Val-Ala-OHHCID 90409067(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-10-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione

생성물 1

HCID 131736461
9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-[[(E)-3-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-[4-(4-methylpiperazin-1-yl)phenyl]-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enyl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
수율 60.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.0541 g, 0.282 mmol, 1.0 eq.) was added to a solution of allylamine 17e (assumed 100% yield, 0.296 g, 0.282 mmol, 1.0 eq.) and HO-Ala-Val-Fmoc 12 (0.116 g, 0.282 mmol, 1.0 eq.) in dry dichloromethane (18 mL). The reaction mixture was stirred for 80 minutes at room temperature when the reaction mixture was diluted with dichloromethane (30 mL) and washed sequentially with water (30 mL) and brine (30 mL). The organic layer was dried over MgSO4 filtered and excess dichloromethane removed under reduced pressure. The resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH) to afford the product as a yellow solid (0.245 g, 60%). LC/MS (2.706 min (ES+)), m/z: 721.5 ½[M+2H]+.

후처리

  1. washwashed sequentially with water (30 mL) and brine (30 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customexcess dichloromethane removed under reduced pressure
  5. customThe resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH)

출처 및 근거

ORD 기록
ord-ff3580e6c9684c618402bbb2c60815af
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09399073B2

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