1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-methyl 2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxylate

HRID 390166

Reaction equation

HRID 390166 reaction equation
Cl.[O:2]=[C:3]1[C:11]2([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:17]([O:19][CH3:20])=[O:18])[CH:9]=2)[NH:4]1.[F:21][C:22]([F:35])([F:34])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1/[CH:29]=[CH:30]/[C:31](O)=[O:32].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[O:2]=[C:3]1[C:11]2([CH2:16][CH2:15][N:14]([C:31](=[O:32])/[CH:30]=[CH:29]/[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[C:22]([F:34])([F:35])[F:21])[CH2:13][CH2:12]2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:17]([O:19][CH3:20])=[O:18])[CH:9]=2)[NH:4]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7196252-(Trifluoromethyl)cinnamic acid, (E)-HCID 67223037Methyl 2-oxospiro[indoline-3,4'-piperidine]-5-carboxylate hydrochloride

Product 1

HCID 58295691(E)-methyl 2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-oxospiro[indoline-3,4′-piperidine]-5-carboxylate hydrochloride (400 mg, 1.46 mmol) in anhydrous CH2Cl2 (10 mL) was added (E)-3-(2-(trifluoromethyl)phenyl)acrylic acid (315 mg, 1.46 mmol), HOBt (394 mg, 2.92 mmol), EDCI (576 mg, 2.92 mmol) and DIEA (942 mg, 7.30 mol) at 0° C. and then stirred overnight at rt under N2. Then the reaction mixture was washed with 1 N aq HCl and water. The organic layer was dried over Na2SO4, filtered and concentrated to afford a residue, which was purified by preparative TLC to give (E)-methyl 2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxylate (328 mg, 49%). 1H NMR (CDCl3): 1.58 (m, 4H), 1.97 (m, 3H), 3.91 (m, 3H), 4.15 (m, 1H), 4.40 (m, 1H), 6.85 (m, 1H), 6.98 (m, 1H), 7.48 (m, 1H), 7.56 (m, 1H), 7.72 (m, 1H), 7.99 (m, 2H).

Workup

  1. washThen the reaction mixture was washed with 1 N aq HCl and water
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford a residue, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-e7a126597de844bea0262f3a66948770
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Linked notes

Loading…