Dimethylformamide → (1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 79652

反応式

HRID 79652 の反応式
[CH3:1][O:2][C:3](=[O:5])[NH2:4].[NH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][NH:36]6)=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1.[CH3:42][O:43][C:44]([NH:46][C@H:47]([C:51]([OH:53])=O)[CH:48]([CH3:50])[CH3:49])=[O:45].CN(C(ON1N=NC2[CH:65]=[CH:66][CH:67]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:78](N(C(C)C)CC)(C)C.CN([CH:90]=[O:91])C>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:5])[NH:4][CH:78]([C:90]([N:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][N:36]6[C:51](=[O:53])[CH:47]([NH:46][C:44]([O:43][CH3:42])=[O:45])[CH:48]([CH3:49])[CH3:50])=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1)=[O:91])[CH:66]([CH3:65])[CH3:67]

参加物

8

反応物 6

HCID 6228DimethylformamideHCID 11722Methyl CarbamateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666205783,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine

生成物 1

HCID 66620472(1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester: To the solution of 3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine (25 mg, 0.035 mmol) and MeOCO-Val-OH (13 mg, 0.074 mmol) in DMF (1.2 ml) was added HATU (28 mg, 0.074 mmol), followed by diisopropylethylamine (61 μl, 0.35 mmol). The mixture was stirred for 90 minutes and was diluted with EtOAc. The organic phase was washed with 1 N NaOH solution, water, and brine, and was dried with sodium sulfate. Concentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O) gave (1-{2-[5-(9-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester (24 mg). m/z: 794.3 (M+H)+, 397.8 (M+2H)+/2. 1H NMR (CD3OD, 300 MHz) δ 8.0-7.9 (8 H, m), 5.27 (2 H, m), 4.3-4.2 (2 H, m), 4.2-3.8 (8 H, m), 3.66 (6 H, s), 3.08 (3 H, s), 2.7-2.5 (2 H, m), 2.4-1.9 (8 H, m), 0.94-0.90 (12 H, m).

後処理

  1. washThe organic phase was washed with 1 N NaOH solution, water, and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O)

出典と根拠

ORDレコード
ord-4156575b80f04585b4d71c4eb6460ce2
出典データセット
uspto-grants-2014_09
特許番号
US08841278B2

関連ノート

読み込み中…