Diisopropylethylamine → 2-[5-(4'-{2-[1-(5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl]-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 79960ノート

反応式

HRID 79960 の反応式
[F:1][C:2]([F:15])([F:14])[CH2:3][CH2:4][C:5]([N:11]=[C:12]=[O:13])(OC)[C:6]([OH:8])=O.CN([C:19]([O:23]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:40]([O:44][C:45]([N:47]1[CH2:51][CH2:50][CH2:49][CH:48]1[C:52]1[NH:53][C:54]([C:57]2[CH:62]=[CH:61][C:60]([C:63]3[CH:68]=[CH:67][C:66]([C:69]4[NH:70][C:71]([CH:74]5[CH2:78][CH2:77][CH2:76][NH:75]5)=[N:72][CH:73]=4)=[CH:65][CH:64]=3)=[CH:59][CH:58]=2)=[CH:55][N:56]=1)=[O:46])([CH3:43])([CH3:42])[CH3:41].C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[C:40]([O:44][C:45]([N:47]1[CH2:51][CH2:50][CH2:49][CH:48]1[C:52]1[NH:53][C:54]([C:57]2[CH:58]=[CH:59][C:60]([C:63]3[CH:68]=[CH:67][C:66]([C:69]4[NH:70][C:71]([CH:74]5[CH2:78][CH2:77][CH2:76][N:75]5[C:6](=[O:8])[CH:5]([NH:11][C:12]([O:23][CH3:19])=[O:13])[CH2:4][CH2:3][C:2]([F:1])([F:14])[F:15])=[N:72][CH:73]=4)=[CH:65][CH:64]=3)=[CH:61][CH:62]=2)=[CH:55][N:56]=1)=[O:46])([CH3:43])([CH3:41])[CH3:42]

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 666204412-{5-[4'-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 866488925,5,5-Trifluoro-2-methoxy-carbonylamino-pentanoic acid

生成物 1

HCID 666209712-[5-(4'-{2-[1-(5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl]-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 59%

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 5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoic acid methyl ester (194 mg, 0.80 mmol) in methanol (3 mL) was added an aqueous LiOH solution (1M, 2 mL, 2 mmol). The resulting solution was stirred at room temperature for 45 minutes 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 clean 5,5,5-Trifluoro-2-methoxy-carbonylamino-pentanoic acid. To a solution of the pentanoic acid in dimethylformamide (2 mL) was added HATU (300 mg, 0.79 mmol). After stirring for 5 minutes, a solution of 2-{5-[4′-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (412 mg, 0.79 mmol) in dimethylformamide (1.9 mL) was added to the reaction, followed immediately by diisopropylethylamine (275 μL, 1.58 mmol). The reaction was stirred for 1 hour at room temperature then diluted with ethyl acetate. The organic layer was washed with water and brine, dried (MgSO4), concentrated and purified by flash chromatography to yield 2-[5-(4′-{2-[1-(5,5,5-trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (340 mg, 59%).

後処理

  1. stirringThe reaction was stirred for 1 hour at room temperature
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash chromatography

出典と根拠

ORDレコード
ord-d0f72875c5e64356897148fe8036ea63
出典データセット
uspto-grants-2014_09
特許番号
US08841278B2

反応ノート

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