Ethanolamine → (E)-N-(2-hydroxyethyl)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamide

HRID 390171Notes

Reaction equation

HRID 390171 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].[NH2:34][CH2:35][CH2:36][OH:37].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[OH:37][CH2:36][CH2:35][NH:34][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:32]

Participants

7

Reactant 5

HCID 700EthanolamineHCID 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 44227074(E)-N-(2-hydroxyethyl)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamideYield 40%

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) was added 2-aminoethanol (3.6 mg, 0.06 mmol), HOBt (12 mg, 0.09 mmol), EDCI (18 mg, 0.09 mmol) and DIEA (28 mg, 0.22 mol) at 0° C. 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)-N-(2-hydroxyethyl)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxamide (8 mg, 40%). 1H NMR (CD3OD): 1.90 (m, 4H), 3.25 (s, 3H), 3.50 (m, 2H), 3.70 (m, 2H), 3.98 (m, 1H), 4.15 (m, 2H), 4.30 (m, 1H), 7.10 (m, 1H), 7.26 (m, 1H), 7.53 (m, 1H), 7.68 (m, 1H), 7.75 (m, 1H), 7.90 (m, 2H), 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-ebfaa152cbbb4368a4c879e73e5e21ae
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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