Diisopropylethylamine → (1-[2-(5-{6-[4-(2-{1-[2-methoxycarbonylamino-2-(tetrahydropyran-4-ylidene)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 2039280ノート

反応式

HRID 2039280 の反応式
[CH3:1][O:2][C:3]([NH:5][C:6](=[C:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[C:7]([OH:9])=O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.Cl.[CH3:43][O:44][C:45](=[O:89])[NH:46][CH:47]([C:51]([N:53]1[CH2:57][CH2:56][CH2:55][CH:54]1[C:58]1[NH:59][C:60]([C:63]2[CH:72]=[CH:71][C:70]3[C:65](=[CH:66][CH:67]=[C:68]([C:73]4[CH:78]=[CH:77][C:76]([C:79]5[NH:80][C:81]([CH:84]6[CH2:88][CH2:87][CH2:86][NH:85]6)=[N:82][CH:83]=5)=[CH:75][CH:74]=4)[CH:69]=3)[CH:64]=2)=[CH:61][N:62]=1)=[O:52])[CH:48]([CH3:50])[CH3:49].C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:43][O:44][C:45](=[O:89])[NH:46][CH:47]([C:51]([N:53]1[CH2:57][CH2:56][CH2:55][CH:54]1[C:58]1[NH:59][C:60]([C:63]2[CH:72]=[CH:71][C:70]3[C:65](=[CH:66][CH:67]=[C:68]([C:73]4[CH:78]=[CH:77][C:76]([C:79]5[NH:80][C:81]([CH:84]6[CH2:88][CH2:87][CH2:86][N:85]6[C:7](=[O:9])[C:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])=[C:10]6[CH2:15][CH2:14][O:13][CH2:12][CH2:11]6)=[N:82][CH:83]=5)=[CH:75][CH:74]=4)[CH:69]=3)[CH:64]=2)=[CH:61][N:62]=1)=[O:52])[CH:48]([CH3:50])[CH3:49]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59611013Methoxycarbonylamino-(tetrahydropyran-4-ylidene)-acetic acidHCID 66620476{2-methyl-1-[2-(5-{6-[4-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester trihydrochloride

生成物 1

HCID 66620834(1-[2-(5-{6-[4-(2-{1-[2-methoxycarbonylamino-2-(tetrahydropyran-4-ylidene)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester収率 50%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of methoxycarbonylamino-(tetrahydropyran-4-ylidene)-acetic acid methyl ester (141 mg, 0.62 mmol) in methanol (1.8 mL) was added an aqueous LiOH solution (1 M, 1.8 mL, 1.8 mmol). The resulting solution was stirred at room temperature for 16 hours and then washed with ethyl acetate. The ethyl acetate washing was discarded and the aqueous layer was acidified with concentrated HCl. The acidified aqueous layer was extracted twice with ethyl acetate. The combined organics were washed with brine, dried (MgSO4), and concentrated to give methoxycarbonylamino-(tetrahydropyran-4-ylidene)-acetic acid. To a solution of methoxycarbonylamino-(tetrahydropyran-4-ylidene)-acetic acid (23 mg, 0.11 mmol) in dimethylformamide (0.6 mL) was added HATU (41 mg, 0.11 mmol). After stirring for 5 minutes, a solution of {2-methyl-1-[2-(5-{6-[4-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester trihydrochloride (50 mg, 0.068 mmol) in dimethylformamide (0.6 mL) was added to the reaction, followed immediately by diisopropylethylamine (85 μL, 0.49 mmol). The reaction was stirred for 1 hour at room temperature then diluted with ethyl acetate. The organic layer was washed successively with saturated aqueous NaHCO3 solution, water and brine, dried (MgSO4), concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 50% ACN/H2O+0.1% HCO2H) to yield {1-[2-(5-{6-[4-(2-{1-[2-methoxycarbonylamino-2-(tetrahydropyran-4-ylidene)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (28 mg, 50%).

後処理

  1. stirringThe reaction was stirred for 1 hour at room temperature
  2. washThe organic layer was washed successively with saturated aqueous NaHCO3 solution, water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by preparative reverse phase HPLC (Gemini, 15 to 50% ACN/H2O+0.1% HCO2H)

出典と根拠

ORDレコード
ord-f439aca5485b4864b90c7a1966a691f8
出典データセット
uspto-grants-2013_11
特許番号
US08575118B2

反応ノート

読み込み中…