Diisopropylethylamine → Ethyl 6-chloro-7-(4-(1-(3-chlorophenyl)pyrrolidin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylate
Reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[CH2:14][CH2:13][CH:12]([NH2:15])[CH2:11]2)[CH:7]=[CH:8][CH:9]=1.C(N(C(C)C)C(C)C)C.[Cl:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][C:37]1[CH:45]=[CH:44][C:40]([C:41](O)=[O:42])=[CH:39][CH:38]=1)[O:32][CH2:31][CH2:30][CH:29]2[C:46]([O:48][CH2:49][CH3:50])=[O:47].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1>ClCCl>[Cl:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][C:37]1[CH:45]=[CH:44][C:40]([C:41](=[O:42])[NH:15][CH:12]3[CH2:13][CH2:14][N:10]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=4)[CH2:11]3)=[CH:39][CH:38]=1)[O:32][CH2:31][CH2:30][CH:29]2[C:46]([O:48][CH2:49][CH3:50])=[O:47]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
Crude 1-(3-chlorophenyl)pyrrolidin-3-amine dihydrochloride (53.7 mg, 0.199 mmol) in dichloromethane was treated sequentially with N-ethyl-N-isopropylpropan-2-amine (78.6 μl, 0.451 mmol), 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1) (50 mg, 0.133 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (30.5 mg, 0.159 mmol), and 1-hydroxy-7-azabenzotriazole (5.42 mg, 0.0398 mmol) at ambient temperature. After 5 hours, the reaction was applied directly to a silica gel column. Elution with a gradient of 20-70% ethyl acetate-hexanes provided the title compound (70 mg, 0.126 mmol, 95.0% yield) as a solid.
Workup
- washElution with a gradient of 20-70% ethyl acetate-hexanes
Sources & evidence
- ORD record
- ord-75f9d1c6001e42d89fcb02737cb6538e
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08716498B2
Reaction notes
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