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Hydrochloric Acid → methyl (S)-1-((2S,4S)-2-(5-(4'-(2-((2S,4S)-1-((R)-2-(cyclopropanecarboxamido)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methylthio)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1751654
ノート
印刷プレビュー

反応式

HRID 1751654 の反応式
C(O[C:6]([NH:8][C@H:9]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C:10]([N:12]1[CH2:16][C@@H:15]([CH2:17][O:18][CH3:19])[CH2:14][C@H:13]1[C:20]1[NH:21][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][C:34]([C:37]4[NH:41][C:40]([C@@H:42]5[CH2:46][C@H:45]([S:47][CH3:48])[CH2:44][N:43]5[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:53])[CH3:52])=[N:39][CH:38]=4)=[CH:33][CH:32]=3)=[CH:27][CH:26]=2)=[CH:23][N:24]=1)=[O:11])=[O:7])(C)(C)C.Cl.[CH:67]1(C(O)=O)[CH2:69][CH2:68]1.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CO.CCOC(C)=O.CN(C=O)C.CO>[CH:67]1([C:6]([NH:8][C@H:9]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C:10]([N:12]2[CH2:16][C@@H:15]([CH2:17][O:18][CH3:19])[CH2:14][C@H:13]2[C:20]2[NH:21][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]4[CH:32]=[CH:33][C:34]([C:37]5[NH:41][C:40]([C@@H:42]6[CH2:46][C@H:45]([S:47][CH3:48])[CH2:44][N:43]6[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:53])[CH3:52])=[N:39][CH:38]=5)=[CH:35][CH:36]=4)=[CH:27][CH:26]=3)=[CH:23][N:24]=2)=[O:11])=[O:7])[CH2:69][CH2:68]1
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 86708799methyl (S)-1-((2S,4S)-2-(5-(4'-(2-((2S,4S)-1-((R)-(tert-butoxycarbonylamino)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methylthio)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

生成物 1

HCID 67682431methyl (S)-1-((2S,4S)-2-(5-(4'-(2-((2S,4S)-1-((R)-2-(cyclopropanecarboxamido)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methylthio)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate収率 20%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 21584119Ethylacetate methanol溶媒

実験手順

Methyl (S)-1-((2S,4S)-2-(5-(4′-(2-((2S,4S)-1-((R)-(tert-butoxycarbonylamino)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methylthio)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (179 mg, 0.20 mmol) was dissolved in DCM (5 mL), MeOH (1 mL) and HCl (4 M in dioxane, 1 mL) was added. The reaction mixture was stirred for 20 h and then concentrated under reduced pressure. The crude residue was treated with cyclopropanecarboxylic acid (16 μL, 0.20 mmol), COMU (96 mg, 0.20 mmol) and DMF (5 mL), then DIPEA (0.17 mL, 1.0 mmol) was added dropwise. After 30 min, the mixture was diluted with 10% MeOH/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 HPLC to afford methyl (S)-1-((2S,4S)-2-(5-(4′-(2-((2S,4S)-1-((R)-2-(cyclopropanecarboxamido)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methylthio)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (34 mg, 20%). LCMS-ESI+: calculated for C48H56N8O6S: 872.40; observed [M+1]+: 874.38.

後処理

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 30 min
  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 HPLC

出典と根拠

ORDレコード
ord-47372b20670245eb8c39ebc8e16271eb
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156823B2

反応ノート

読み込み中…

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