Hydrochloric Acid → [2-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-pyran-4-ylmethyl)-ethyl]-carbamic acid methyl ester

HRID 1751454ノート

反応式

HRID 1751454 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[NH:35][C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:57])[CH:45]([NH:52][C:53]([O:55][CH3:56])=[O:54])[C:46]6[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=6)=[N:37][CH:38]=5)=[CH:30][CH:29]=4)[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.Cl.[CH3:59][O:60][C:61]([NH:63][CH:64]([CH2:68][CH:69]1[CH2:74][CH2:73][O:72][CH2:71][CH2:70]1)[C:65]([OH:67])=O)=[O:62].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH3:59][O:60][C:61](=[O:62])[NH:63][CH:64]([CH2:68][CH:69]1[CH2:74][CH2:73][O:72][CH2:71][CH2:70]1)[C:65]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:28]4[CH:29]=[CH:30][C:31]([C:34]5[NH:35][C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:57])[CH:45]([NH:52][C:53]([O:55][CH3:56])=[O:54])[C:46]6[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=6)=[N:37][CH:38]=5)=[CH:32][CH:33]=4)[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=[O:67]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 696729572-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-propionic acidHCID 696730252-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 77335531[2-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-pyran-4-ylmethyl)-ethyl]-carbamic acid methyl ester収率 18.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.12 g, 0.15 mmol) in CH2Cl2 (1.5 mL) and MeOH (0.2 mL) was added HCl (in dioxanes, 4 M, 0.75 mL, 3.0 mmol). The solution was stirred at room temperature for 2 h and concentrated to dryness. The resulting solid was dissolved in DMF (1.5 mL). 2-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-propionic acid (0.05 g, 0.22 mmol), HATU (0.07 g, 0.19 mmol) and DIPEA (0.13 mL, 0.74 mmol) were added. The resulting solution was stirred at room temperature for 18 h. The solution was purified twice by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% TFA)) and lyophilized to provide [2-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-pyran-4-ylmethyl)-ethyl]-carbamic acid methyl ester (0.024 g, 18%). LCMS-ESI+: calc'd for C50H54N8O7: 878.41 (M+); Found: 879.97 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. dissolutionThe resulting solid was dissolved in DMF (1.5 mL)
  3. stirringThe resulting solution was stirred at room temperature for 18 h
  4. customThe solution was purified twice by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% TFA))

出典と根拠

ORDレコード
ord-73312bd0a81b456191b9485b0f6c5d45
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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