1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 9H-fluoren-9-ylmethyl N-[(2R)-1-[[(2S)-1-[[(E)-3-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-methyl-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 1057078노트

반응식

HRID 1057078 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:71][CH3:72])=[CH:48][C:49]5[C:55](=[O:56])[N:54]6[CH:57]=[C:58]([CH3:60])[CH2:59][C@H:53]6[C:52](=[O:61])[N:51]([CH2:62][O:63][CH2:64][CH2:65][Si:66]([CH3:69])([CH3:68])[CH3:67])[C:50]=5[CH:70]=4)[C:37]([O:39][CH3:40])=[CH:38][C:22]=3[C:21](=[O:73])[N:20]2[CH:74]=1.[CH:75]1[C:87]2[CH:86]([CH2:88][O:89][C:90]([NH:92][C@@H:93]([CH:102]([CH3:104])[CH3:103])[C:94]([NH:96][C@@H:97]([CH3:101])[C:98](O)=[O:99])=[O:95])=[O:91])[C:85]3[C:80](=[CH:81][CH:82]=[CH:83][CH:84]=3)[C:79]=2[CH:78]=[CH:77][CH:76]=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:71][CH3:72])=[CH:48][C:49]3[C:55](=[O:56])[N:54]4[CH:57]=[C:58]([CH3:60])[CH2:59][C@H:53]4[C:52](=[O:61])[N:51]([CH2:62][O:63][CH2:64][CH2:65][Si:66]([CH3:68])([CH3:67])[CH3:69])[C:50]=3[CH:70]=2)=[CH:35][C:23]2[N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:34])[CH3:33])[C:25](=[O:26])[C@@H:19]3[CH2:18][C:17](/[CH:16]=[CH:15]/[CH2:14][NH:13][C:98](=[O:99])[C@@H:97]([NH:96][C:94](=[O:95])[C@H:93]([NH:92][C:90](=[O:91])[O:89][CH2:88][CH:86]4[C:87]5[CH:75]=[CH:76][CH:77]=[CH:78][C:79]=5[C:80]5[C:85]4=[CH:84][CH:83]=[CH:82][CH:81]=5)[CH:102]([CH3:104])[CH3:103])[CH3:101])=[CH:74][N:20]3[C:21](=[O:73])[C:22]=2[CH:38]=1

참가 물질

5

반응물 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11165770Fmoc-Val-Ala-OHHCID 90407865(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-methyl-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 1317364599H-fluoren-9-ylmethyl N-[(2R)-1-[[(2S)-1-[[(E)-3-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-methyl-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]carbamate수율 41%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.018 g, 0.095 mmol, 1.0 eq.) was added to a solution of allylamine 17a (assumed 100% yield, 0.100 g, 0.095 mmol, 1.0 eq.) and HO-Ala-Val-Fmoc 12 (0.036 g, 0.095 mmol, 1.0 eq.) in dry dichloromethane (6 mL). The reaction mixture was stirred for 120 minutes at room temperature when the reaction mixture was diluted with dichloromethane (10 mL) and washed sequentially with water (10 mL) and brine (10 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; 100:1 v/v DCM/MeOH to 40:1 v/v DCM/MeOH) to afford the product as a yellow solid (0.050 g, 35%). LC/MS (3.677 min (ES+)), m/z: 1281.42 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, 2H, J=7.7 Hz), 7.58 (m, 2H), 7.40 (t, 2H, J=7.6 Hz), 7.34 (d, 2H, J=5.7 Hz), 7.31 (m, 3H), 7.25 (m, 2H), 6.93 (s, 1H), 6.68 (m, 1H), 6.34 (m, 3H), 5.58 (m, 1H), 5.49 (m, 2H), 4.71 (m, 2H), 4.45 (m, 5H), 4.27 (m, 4H), 4.22 (t, 1H, J=7.0 Hz), 3.97 (m, 2H), 3.89 (m, 7H), 3.75 (m, 2H), 3.65 (m, 3H), 3.44 (m, 1H), 2.77 (m, 2H), 2.43 (m, 2H), 2.14 (m, 1H), 1.83 (d, 3H, J=1.0 Hz), 1.40 (d, 3H, J=6.9 Hz), 0.99-0.91 (m, 10H), 0.01 (s, 9H), 0.00 (s, 9H).

후처리

  1. washwashed sequentially with water (10 mL) and brine (10 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; 100:1 v/v DCM/MeOH to 40:1 v/v DCM/MeOH)

출처 및 근거

ORD 기록
ord-758f38aa81794056943047559f520a70
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09399073B2

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