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

HRID 390170Notes

Reaction equation

HRID 390170 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].C1C=CC2N(O)N=[N:40]C=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]([NH2:40])=[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:20])([F:22])[F:21])[CH2:6][CH2:5]2)[C:3]1=[O:33]

Participants

6

Reactant 4

HCID 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 58295665(E)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamideYield 10.5%

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 (15 mg, 0.05 mmol) in anhydrous CH2Cl2 (4 mL) was added HOBt (15 mg, 4 mL), EDCI (22 mg, 0.11 mmol) and DIEA (32 mg, 0.25 mmol) at 0° C. and the mixture was stirred overnight under NH3 at rt. The reaction mixture was washed with 1 N aq HCl and the aqueous phase was extracted with CH2Cl2 (2×). The combined organic phases were dried, filtered and concentrated to give (E)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxamide (2.4 mg, 10%). 1H NMR (CD3OD): 1.94 (m, 4H), 3.27 (s, 3H), 4.01 (m, 1H), 4.28 (m, 3H), 7.10 (d, 1H), 7.26 (d, 1H), 7.55 (m, 1H), 7.66 (m, 1H), 7.76 (m, 1H), 8.00 (m, 4H).

Workup

  1. washThe reaction mixture was washed with 1 N aq HCl
  2. extractionthe aqueous phase was extracted with CH2Cl2 (2×)
  3. customThe combined organic phases were dried
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8d40fc7db7d643d895cb21446d2fa1e6
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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