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 1057078ノート

反応式

HRID 1057078 の反応式
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

参加物

5

反応物 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

生成物 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]carbamate収率 41%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-758f38aa81794056943047559f520a70
出典データセット
uspto-grants-2016_07
特許番号
US09399073B2

反応ノート

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