1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.Cl.[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][NH:24][CH2:23]2.C(N=C=NCCCN(C)C)C>ClCCl>[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:14](=[O:16])[CH2:13][N:10]1[CH2:11][CH2:12][CH:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9]1=[O:17])[CH2:23]2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 2-(3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.053 g, 0.223 mmol; Example 216A) and 5-fluoroisoindoline hydrogen chloride (0.043 g, 0.246 mmol) in dichloromethane (0.4 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.059 mL, 0.335 mmol) and the reaction stirred for 18 hours. The reaction was loaded onto a GraceResolv™ 12 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.34-7.16 (m, 4H), 7.08-6.93 (m, 3H), 4.82 (dd, J=8.6, 16.1, 4H), 4.27 (d, J=16.2, 1H), 4.15 (d, J=16.2, 1H), 3.79-3.59 (m, 3H), 2.67-2.51 (m, 1H), 2.18 (ddd, J=8.5, 12.9, 16.1, 1H); MS (ESI+) m/z 357.0 (M+H)+.
Workup
- washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes
Sources & evidence
- ORD record
- ord-79cd6e8e23734f67b9e353eb6d1e33fc
- Source dataset
- uspto-grants-2011_10
- Patent number
- US08044069B2
Reaction notes
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