1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-1-methyl-5-(4-methylpiperazine-1-carbonyl)-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidin]-2-one

HRID 390172Notes

Reaction equation

HRID 390172 reaction equation
[CH3:1][N:2]1[C:29]2[C:24](=[CH:25][C:26]([C:30]([OH:32])=O)=[CH:27][CH:28]=2)[C:4]2([CH2:9][CH2:8][N:7]([C:10](=[O:23])/[CH:11]=[CH:12]/[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[CH2:6][CH2:5]2)[C:3]1=[O:33].[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.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:29]2[C:24](=[CH:25][C:26]([C:30]([N:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)=[O:32])=[CH:27][CH:28]=2)[C:4]2([CH2:9][CH2:8][N:7]([C:10](=[O:23])/[CH:11]=[CH:12]/[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[CH2:6][CH2:5]2)[C:3]1=[O:33]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58295682(E)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxylic acid

Product 1

HCID 58295676(E)-1-methyl-5-(4-methylpiperazine-1-carbonyl)-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidin]-2-oneYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (E)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxylic acid (20 mg, 0.04 mmol) in anhydrous CH2Cl2 (5 mL) at 0° C. was added 1-methyl-piperazine (6.0 mg, 0.06 mmol), HOBt (12 mg, 0.09 mmol), EDCI (18 mg, 0.09 mmol) and DIEA (28 mg, 0.22 mol) and the mixture was stirred overnight at rt under N2. The reaction mixture was washed with 1 N aq HCl and water. The organic phase was dried over Na2SO4, filtered and concentrated to afford a residue, which was purified by prep TLC to give (E)-1-methyl-5-(4-methylpiperazine-1-carbonyl)-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidin]-2-one (12 mg, 57%). 1H NMR (CD3OD): 1.90 (m, 4H), 2.95 (s, 3H), 3.30 (m, 11H), 3.95 (m, 1H), 4.20 (m, 2H), 4.30 (m, 1H), 7.10 (m, 1H), 7.26 (m, 1H), 7.50 (m, 3H), 7.66 (m, 1H), 7.77 (m, 1H), 8.00 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-763903a81b6a44d9aa6dcc8be2f952b9
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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