Diisopropylethylamine → N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide
反応式
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([OH:31])=O)[N:28]=1.[C@H:39]12[CH2:45][C@H:42]([CH2:43][CH2:44]1)[C@@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:52])([F:51])[F:50])[NH:40]2.CCN(C(C)C)C(C)C>CN(C=O)C.CC(OC)(C)C>[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([N:40]2[C@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:51])([F:52])[F:50])[C@@H:42]3[CH2:45][C@H:39]2[CH2:44][CH2:43]3)=[O:31])[N:28]=1参加物
7
反応物 4
生成物 1
試薬・触媒・溶媒 2
実験手順
TBTU (1.70 mmol, 1.10 eq) is added to a solution of 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid (1.62 mmol, 1.05 eq), N-[(1R,3S,4S)-1-(2-Aza-bicyclo[2.2.1]hept-3-yl)methyl]-2,2,2-trifluoro-acetamide (1.55 mmol, 1.0 eq) and DIPEA (5.41 mmol, 3.5 eq) in DMF (10 mL). After 90 min the mixture is diluted with TBME (50 mL) and washed three times with an aq. NaOH solution (0.5 M, 50 mL each). The combined aq. layers are extracted twice with TBME (30 mL each). The organic layers are combined, washed with water (3×30 mL) and brine (30 mL), dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.82 min; [M+H]+=442.9.
後処理
- washwashed three times with an aq. NaOH solution (0.5 M, 50 mL each)
- extractionThe combined aq. layers are extracted twice with TBME (30 mL each)
- washwashed with water (3×30 mL) and brine (30 mL)
- dry with materialdried over MgSO4
- concentrationconcentrated in vacuo
出典と根拠
- ORDレコード
- ord-ea3351da984e48ac9d25900e0e2c29b5
- 出典データセット
- uspto-grants-2012_08
- 特許番号
- US08236801B2
反応ノート
読み込み中…