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

HRID 1751444ノート

反応式

HRID 1751444 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]([CH:68]1[CH2:73][CH2:72][O:71][CH2:70][CH2:69]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.C1COCC1.[Li+].[OH-]>[CH3:56][O:55][C:53](=[O:54])[NH:52][CH:45]([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)[C:44]([N:40]1[CH2:41][CH2:42][CH2:43][CH:39]1[C:36]1[NH:35][C:34]([C:31]2[CH:32]=[CH:33][C:28]([C:23]3[CH:22]=[CH:21][C:20]4[C:25](=[CH:26][CH:27]=[C:18]([C:15]5[NH:14][C:13]([CH:9]6[CH2:10][CH2:11][CH2:12][N:8]6[C:65](=[O:67])[CH:64]([NH:63][C:61]([O:60][CH3:59])=[O:62])[CH:68]6[CH2:73][CH2:72][O:71][CH2:70][CH2:69]6)=[N:17][CH:16]=5)[CH:19]=4)[CH:24]=3)=[CH:29][CH:30]=2)=[CH:38][N:37]=1)=[O:57]

参加物

10

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 585162412-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic 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 69672814{2-[2-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl}-carbamic acid methyl ester収率 37%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 3939Lithium Hydroxide溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran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 (0.20 g, 0.26 mmol) in CH2Cl2 (2.5 mL) and MeOH (0.1 mL) was added HCl (in dioxanes, 4 M, 0.7 mL, 2.80 mmol). The solution was stirred at room temperature for 3 h and concentrated to dryness. The resulting solid was slurried in CH2Cl2 (4 mL). Methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (0.12 g, 0.54 mmol), HATU (0.12 g, 0.33 mmol), and DIPEA (0.2 mL, 1.15 mmol) were added. The resulting solution was stirred at room temperature for 1 h. The solution was diluted with THF and LiOH (2.5 M, 0.1 mL) was added. The solution was concentrated to dryness and the crude oil was diluted with DMF and purified by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% formic acid)) and lyophilized to provide {2-[2-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl}-carbamic acid methyl ester (0.083 g, 37%). LCMS-ESI+: calc'd for C49H52N8O7: 864.40 (M+); Found: 866.01 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. stirringThe resulting solution was stirred at room temperature for 1 h
  3. additionwas added
  4. concentrationThe solution was concentrated to dryness
  5. additionthe crude oil was diluted with DMF
  6. custompurified by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% formic acid))

出典と根拠

ORDレコード
ord-1cba050c9ceb432a8b695189b03e1d8f
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…