Hydrochloric Acid → (2S,4S)-benzyl 2-(5-(4'-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxamido)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate

HRID 1751651ノート

反応式

HRID 1751651 の反応式
C([O:5][C:6]([NH:8][CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:28][C:27]([C@@H:29]4[CH2:33][C@H:32]([CH2:34][O:35][CH3:36])[CH2:31][N:30]4[C:37]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[O:38])=[N:26][CH:25]=3)=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)=[O:11])=O)(C)(C)C.Cl.[CH3:48][O:49][C:50]([NH:52][C@@H:53]([CH:66]([CH3:68])[CH3:67])[C:54]([N:56]1[CH2:60][C@@H:59]([S:61][CH3:62])[CH2:58][C@H:57]1C(O)=O)=[O:55])=[O:51].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.CCOC(C)=O.CN(C=O)C.CO>[CH3:48][O:49][C:50]([NH:52][C@@H:53]([CH:66]([CH3:68])[CH3:67])[C:54]([N:56]1[CH2:60][C@@H:59]([S:61][CH3:62])[CH2:58][C@H:57]1[C:6]([NH:8][CH2:9][C:10]([C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:28][C:27]([C@@H:29]4[CH2:33][C@H:32]([CH2:34][O:35][CH3:36])[CH2:31][N:30]4[C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[O:38])=[N:26][CH:25]=3)=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)=[O:11])=[O:5])=[O:55])=[O:51]

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 67682555HCID 67682555、化合物HCID 69671862(2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxylic acid

生成物 1

HCID 67682446(2S,4S)-benzyl 2-(5-(4'-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxamido)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate収率 58%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(2S,4S)-benzyl 2-(5-(4′-(2-(tert-butoxycarbonylamino)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (640 mg, 1.02 mmol) was dissolved in DCM (8 mL), MeOH (2 mL) and HCl (4 M in dioxane, 2 mL) was added. The reaction mixture was stirred for 14 h and then concentrated under reduced pressure. The crude residue was treated with (2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxylic acid (324 mg, 1.02 mmol), HATU (388 mg, 1.02 mmol) and DMF (10 mL), then DIPEA (0.9 mL, 5.12 mmol) was added dropwise. After 1 h, the mixture was diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford (2S,4S)-benzyl 2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxamido)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (487 mg, 58%).

後処理

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 1 h
  3. washwashed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-3a24ab97abb947a1bfa4195a714c69b5
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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