1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[isoindoline-1,4'-piperidin]-3-one

HRID 390162Notes

Reaction equation

HRID 390162 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:15]=1[C:9]1([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[NH:8][C:7]2=[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].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:15]=1[C:9]1([CH2:10][CH2:11][N:12]([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])[CH2:13][CH2:14]1)[NH:8][C:7]2=[O:16]

Participants

6

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 749393-(2-(Trifluoromethyl)phenyl)-2-propenoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 582957267-Bromospiro[isoindoline-1,4'-piperidin]-3-one

Product 1

HCID 58295735(E)-7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[isoindoline-1,4'-piperidin]-3-oneYield 2.3%

Procedure

A mixture of 7-bromospiro[isoindoline-1,4′-piperidin]-3-one (194 mg, 0.69 mmol), 3-(2-(trifluoromethyl)phenyl)acrylic acid (100 mg, 0.46 mmol), EDCI (181 mg, 0.92 mmol), HOBt (124 mg, 0.92 mmol) and i-Pr2NEt (1 mL) was stirred at rt overnight. The mixture was washed with 5% aq HCl, and the organic layer was concentrated to give a residue which was purified by preparative HPLC to afford (E)-7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[isoindoline-1,4′-piperidin]-3-one (5 mg, 2%). 1H NMR (400 MHz, CDCl3): δ=1.53 (m, 2H), 2.98 (m, 3H), 3.42 (m, 1H), 4.23 (m, 1H), 4.50 (m, 1H), 4.93 (m, 1H), 6.80 (m, 1H), 7.33 (m, 1H), 7.40 (m, 1H), 7.50 (m, 1H), 7.65 (m, 3H), 7.77 (m, 1H), 7.95 (m, 1H), 8.50 (m, 1H).

Workup

  1. washThe mixture was washed with 5% aq HCl
  2. concentrationthe organic layer was concentrated
  3. customto give a residue which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-a2260e92613a40ba80793dd472b1deaf
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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