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
Reaction equation
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]=1Participants
Reactant 3
HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride
HCID 11165770Fmoc-Val-Ala-OH
HCID 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)-dioneProduct 1
Reagents, catalysts & solvents 1
Procedure
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]+.
Workup
- washwashed sequentially with water (30 mL) and brine (30 mL)
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- customexcess dichloromethane removed under reduced pressure
- customThe resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH)
Sources & evidence
- ORD record
- ord-ff3580e6c9684c618402bbb2c60815af
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09399073B2
Reaction notes
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