1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-1-methyl-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidin]-2-one
Reaction equation
[CH3:1][N:2]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:4]2([CH2:9][CH2:8][NH:7][CH2:6][CH2:5]2)[C:3]1=[O:16].[F:17][C:18]([F:31])([F:30])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH:25]=[CH:26][C:27](O)=[O:28].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:1][N:2]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:4]2([CH2:9][CH2:8][N:7]([C:27](=[O:28])/[CH:26]=[CH:25]/[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[C:18]([F:30])([F:31])[F:17])[CH2:6][CH2:5]2)[C:3]1=[O:16]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 1-methylspiro[indoline-3,4′-piperidin]-2-one (100 mg, 0.46 mmol) in CH2Cl2 (5 mL) was added 3-(2-trifluoromethyl-phenyl)-acrylic acid (120 mg, 0.56 mmol), HOBt (124 mg, 0.92 mmol), EDCI (181 mg, 0.92 mmol) and DIEA (297 mg, 2.30 mmol). The reaction mixture was stirred at rt overnight. The above mixture was concentrated and the residue was purified by preparative HPLC to give (E)-1-methyl-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidin]-2-one (50 mg, 26%). 1H NMR (CDCl3): 1.85-2.00 (m, 4H), 3.72 (s, 3H), 3.90-4.00 (m, 2H), 4.15-4.30 (m, 1H), 4.40-4.50 (m, 1H), 6.80-6.90 (m, 2H), 7.10-7.15 (m, 1H), 7.25-7.35 (m, 2H), 7.45-7.60 (m, 2H), 7.68-7.72 (m, 2H), 7.91-8.00 (m, 1H).
Workup
- concentrationThe above mixture was concentrated
- customthe residue was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-cb66094fe46546bbbcae16010d6ecbea
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08383629B2
Reaction notes
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