Diisopropylethylamine → HCID 178502431、化合物

HRID 1625496ノート

反応式

HRID 1625496 の反応式
Cl.[CH3:2][O:3][C:4](=[O:51])[N:5](C)[C@H:6]([C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][NH:45]6)[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:29][CH:28]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])[CH:7]([CH3:9])[CH3:8].[CH3:52][O:53][C:54]([N:56]([CH3:64])[C@@H:57]([CH:61]([CH3:63])[CH3:62])[C:58]([OH:60])=O)=[O:55].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>CN(C=O)C.O>[CH3:2][O:3][C:4]([NH:5][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:28]=[CH:29][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][N:45]6[C:58](=[O:60])[C@@H:57]([N:56]([CH3:64])[C:54](=[O:55])[O:53][CH3:52])[CH:61]([CH3:63])[CH3:62])[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:31][CH:32]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])=[O:51]

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 59166373N-(Methoxycarbonyl)-N-methyl-L-valineHCID 178502120HCID 178502120、化合物

生成物 1

HCID 178502431HCID 178502431、化合物収率 43.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of methyl {(S)-2-methyl-1-[(2S,4S)-4-methyl-2-(5-{4′-[2-((2S,4S)-4-methyl-pyrrolidin-2-yl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester hydrochloride (68.7 mg, 0.0987 mmol) and (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (18.67 mg, 0.09867 mmol) in DMF (2 mL), cooled in an ice bath is sequentially added HATU (41.25 mg, 0.1085 mmol) and DIPEA (38.26 mg, 51.56 μL, 0.2960 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 5 hours, and diluted with water (6 mL). The mixture is extracted with EtOAc (5×6 mL), and the combined organic layers are washed with H2O (3×3 mL), dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give methyl ((S)-1-((2S,4S)-2-(4-(4′-(2-((2S,4S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-4-methylpyrrolidin-2-yl)-3H-benzo[d]imidazol-6-yl)-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate (36 mg, 41%).

後処理

  1. extractionThe mixture is extracted with EtOAc (5×6 mL)
  2. washthe combined organic layers are washed with H2O (3×3 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2)
  7. customis further purified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-acbcc9b13f2a422bb0a069f0ad4f06a1
出典データセット
uspto-grants-2014_07
特許番号
US08779156B2

反応ノート

読み込み中…