1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-{1'-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}acetamide

HRID 545167Notes

Reaction equation

HRID 545167 reaction equation
[CH3:1][CH2:2][N:3]=C=NCCCN(C)C.[OH:12]C(C(F)(F)F)=O.[O:19]=[C:20]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32](CC(N)=O)[CH:33]=2)[O:28][C:22]2([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:21]1.[CH3:39][O:40][C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[N:44]=[C:43]([C:51]([OH:53])=O)[CH:42]=1.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCN(CC)CC>[CH3:39][O:40][C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[N:44]=[C:43]([C:51]([N:25]2[CH2:24][CH2:23][C:22]3([CH2:21][C:20](=[O:19])[C:34]4[C:29](=[CH:30][CH:31]=[C:32]([NH:3][C:2](=[O:12])[CH3:1])[CH:33]=4)[O:28]3)[CH2:27][CH2:26]2)=[O:53])[CH:42]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5945964-Methoxy-2-quinolinecarboxylic acidHCID 866101694-oxospiro[chroman-2,4'-piperidin]-6-ylacetamide TFA salt

Product 1

HCID 16041575N-{1'-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

63.3 g of EDCI was added to a mixture of 16.5 g of 4-oxospiro[chroman-2,4′-piperidin]-6-ylacetamide TFA salt, 61.0 g of 4-methoxyquinoline-2-carboxylic acid, 45.9 g of HOBT, 50 mL of Et3N and 90 mL DMF, at 0° C., and the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water and aqueous saturated sodium carbonate solution successively, then dried over sodium sulfate, and then concentrated. The residue was purified through silica gel column chromatography (eluted with 3% MeOH/CHCl3), and the intended compound was obtained. 1H-NMR (300 MHz, CDCl3) δ: 8.21 (1H, dd, J=8.5, 1.3 Hz), 7.99 (1H, dd, J=8.5, 1.0 Hz), 7.94 (1H, dd, J=8.9, 2.7 Hz), 7.73 (1H, ddd, J=8.5, 6.9, 1.3 Hz), 7.67 (1H, d, J=2.7 Hz), 7.55 (1H, ddd, J=8.5, 6.9, 1.0 Hz), 7.34 (1H, br.s), 7.09 (1H, s), 7.01 (1H, d, J=8.9 Hz), 4.65-4.55 (1H, m), 4.09 (3H, s), 4.06-3.96 (1H, m), 3.58 (1H, dt, J=2.9, 12.7 Hz), 3.36 (1H, dt, J=2.9, 12.7 Hz), 2.83-2.69 (2H, m), 2.26-2.12 (1H, m), 2.17 (3H, s), 2.10-2.00 (1H, m), 1.96-1.75 (2H, m). MS [M+H]+=460.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and aqueous saturated sodium carbonate solution successively
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified through silica gel column chromatography (eluted with 3% MeOH/CHCl3)
  7. customthe intended compound was obtained

Sources & evidence

ORD record
ord-5d49bbfb7f854e2aa5addb337e4cf174
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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