1,2-Dichloroethane → (4S)-tert-butyl 3-((8-carbamoylquinolin-5-yl)carbamoyl)-4-(3-fluorophenyl)pyrrolidine-1-carboxylate
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][C@@H:9]2[C:20]([O-:22])=O)[CH:5]=[CH:6][CH:7]=1.ClCCCl.CCN(C(C)C)C(C)C.[NH2:36][C:37]1[CH:46]=[CH:45][C:44]([C:47]([NH2:49])=[O:48])=[C:43]2[C:38]=1[CH:39]=[CH:40][CH:41]=[N:42]2>>[C:47]([C:44]1[CH:45]=[CH:46][C:37]([NH:36][C:20]([CH:9]2[C@@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:10]2)=[O:22])=[C:38]2[C:43]=1[N:42]=[CH:41][CH:40]=[CH:39]2)(=[O:48])[NH2:49]Participants
Reactant 4
Product 1
Procedure
To a solution of tert-butyl(3R,4S)-4-(3-fluoro-phenyl)-pyrrolidine-1,3-dicarboxylate (125.00 mg; 0.40 mmol; 1.00 eq.) in DCE (4.0 ml) bis(2-oxo-1,3-oxazolidin-3-yl)phosphinic chloride (102.87 mg; 0.40 mmol; 1.00 eq.) was added. After stirring for 15 mins at RT, DIEA (0.15 ml; 0.81 mmol; 2.00 eq.) and 5-aminoquinoline-8-carboxamide (75.65 mg; 0.40 mmol; 1.00 eq) were added. The reaction mixture was stirred overnight at 60° C. The crude was purified by prep HPLC to yield (4S)-tert-butyl 3-((8-carbamoylquinolin-5-yl)carbamoyl)-4-(3-fluorophenyl)pyrrolidine-1-carboxylate, which was added 1 ml 4.0M HCl and 1 ml methanol, stirred at RT for 3 h. The reaction mixture was concentrated, neutralized to Ph 7 and purified by prep HPLC to afford Example 27. (M+H=479, obsd=479).
Workup
- stirringThe reaction mixture was stirred overnight at 60° C
- customThe crude was purified by prep HPLC
Sources & evidence
- ORD record
- ord-200b96c89a464cbabfdbbb00a7645b75
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139568B2
Reaction notes
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