Dimethylamine, hydrochloride → (E)-N,N,1-trimethyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamide

HRID 390169Notes

Reaction equation

HRID 390169 reaction equation
[CH3:1][N:2]1[C:29]2[C:24](=[CH:25][C:26]([C:30](O)=[O:31])=[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].C[CH2:35][N:36]=[C:37]=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.N(C)C.Cl>C(Cl)Cl>[CH3:35][N:36]([CH3:37])[C:30]([C:26]1[CH:25]=[C:24]2[C:4]3([CH2:5][CH2:6][N:7]([C:10](=[O:23])/[CH:11]=[CH:12]/[C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[C:19]([F:22])([F:21])[F:20])[CH2:8][CH2:9]3)[C:3](=[O:33])[N:2]([CH3:1])[C:29]2=[CH:28][CH:27]=1)=[O:31]

Participants

7

Reactant 5

HCID 10473Dimethylamine, hydrochlorideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 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 58295794(E)-N,N,1-trimethyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamideYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (E)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxylic acid (20 mg, 0.508 mmol), EDCI (18 mg, 0.088 mmol), HOBt (12 mg, 0.088 mmol), and DIEA (60 mg, 0.44 mmol) in CH2Cl2 was added NHMe2.HCl (16 mg, 0.176 mmol) at 0° C. The mixture was stirred at rt overnight. The mixture was concentrated to give the crude product, which was purified by preparative TLC to give (E)-N,N,1-trimethyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxamide (6 mg, 14%). 1H NMR (400 MHz, CDCl3): δ=3.05 (m, 6H), 3.25 (m, 3H), 3.60-3.75 (m, 2H), 3.95 (m, 2H), 4.15 (m, 1H), 4.35 (m, 1H), 6.85 (m, 1H), 7.35 (m, 1H), 7.45 (m, 2H), 7.55 (m, 1H) 7.70 (m, 2H), 8.00 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. customto give the crude product, which
  3. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-450488b86c8148f7b658a8292c3e93b6
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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