Hydrochloric Acid → Methyl (4R)-1-[(2S)-2-cyclohexyl-2-({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetyl]-4-[(7-methoxy-2-oxo-6-vinyl-1,2-dihydroquinolin-4-yl)oxy]-L-prolinate

HRID 1423376ノート

反応式

HRID 1423376 の反応式
Cl.[CH3:2][O:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([O:15][C@H:16]3[CH2:20][NH:19][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17]3)=[CH:9][C:10](=[O:14])[NH:11]2)=[CH:6][C:5]=1[CH:25]=[CH2:26].[CH:27]1([C@H:33]([NH:37][C:38]([O:40][CH2:41][C:42]([CH3:47])([CH3:46])[CH2:43][CH:44]=[CH2:45])=[O:39])[C:34](O)=[O:35])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.CCOC(C)=O>[CH:27]1([C@H:33]([NH:37][C:38]([O:40][CH2:41][C:42]([CH3:47])([CH3:46])[CH2:43][CH:44]=[CH2:45])=[O:39])[C:34]([N:19]2[CH2:20][C@H:16]([O:15][C:8]3[C:7]4[C:12](=[CH:13][C:4]([O:3][CH3:2])=[C:5]([CH:25]=[CH2:26])[CH:6]=4)[NH:11][C:10](=[O:14])[CH:9]=3)[CH2:17][C@H:18]2[C:21]([O:23][CH3:24])=[O:22])=[O:35])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1

参加物

8

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 57617041(2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acidHCID 86643488Methyl (4R)-4-[(7-methoxy-2-oxo-6-vinyl-1,2-dihydroquinolin-4-yl)oxy]-L-prolinate hydrochloride

生成物 1

HCID 59279821Methyl (4R)-1-[(2S)-2-cyclohexyl-2-({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetyl]-4-[(7-methoxy-2-oxo-6-vinyl-1,2-dihydroquinolin-4-yl)oxy]-L-prolinate収率 119.9%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of the product from Step 4, methyl (4R)-4-[(7-methoxy-2-oxo-6-vinyl-1,2-dihydroquinolin-4-yl)oxy]-L-prolinate hydrochloride (0.84 g, 2.206 mmol) and linker B20, (2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid (0.689 g, 2.316 mmol) in DMF (2 mL) was added DIPEA (1.156 mL, 6.62 mmol) and HATU (1.090 g, 2.87 mmol). After 15 min, the reaction was complete and 1 N HCl and EtOAc were added. The organic layer was washed with water and brine, dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified on silica (gradient elution, 0-5% MeOH/DCM) to yield 1.65 g of material which still contained HATU residue. This was removed by extracting the material with EtOAc and 1N HCl (4×), water (1×) and brine (1×). The organic layer was dried over MgSO4 and the solvent was removed in vacuo to yield 1.13 g (82%) of the title compound. LRMS ESI+(M+H)+ 624.6.

後処理

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried over MgSO4
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified on silica (gradient elution, 0-5% MeOH/DCM)

出典と根拠

ORDレコード
ord-1eb36b68168a48e79eb4e63ebbc43a5e
出典データセット
uspto-grants-2015_01
特許番号
US08927569B2

反応ノート

読み込み中…