1-Hydroxybenzotriazole → N-carbamoylmethyl-1'-[(1-cyclopropyl-4-ethoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

HRID 420127Notes

Reaction equation

HRID 420127 reaction equation
Cl.[C:2]([CH2:5][NH:6][C:7]([C:9]1[CH:10]=[C:11]2[C:21](=[CH:22][CH:23]=1)[O:20][C:14]1([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)[CH2:13][C:12]2=[O:24])=[O:8])(=[O:4])[NH2:3].[CH:25]1([N:28]2[C:36]3[C:31](=[C:32]([O:40][CH2:41][CH3:42])[CH:33]=[C:34]([C:37](O)=[O:38])[CH:35]=3)[CH:30]=[CH:29]2)[CH2:27][CH2:26]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[C:2]([CH2:5][NH:6][C:7]([C:9]1[CH:10]=[C:11]2[C:21](=[CH:22][CH:23]=1)[O:20][C:14]1([CH2:19][CH2:18][N:17]([C:37]([C:34]3[CH:35]=[C:36]4[C:31]([CH:30]=[CH:29][N:28]4[CH:25]4[CH2:27][CH2:26]4)=[C:32]([O:40][CH2:41][CH3:42])[CH:33]=3)=[O:38])[CH2:16][CH2:15]1)[CH2:13][C:12]2=[O:24])=[O:8])(=[O:4])[NH2:3]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 666493891-cyclopropyl-4-ethoxy-1H-indole-6-carboxylic acidHCID 66649519N-Carbamoylmethyl-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide hydrochloride

Product 1

HCID 24965038N-carbamoylmethyl-1'-[(1-cyclopropyl-4-ethoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

N-Carbamoylmethyl-4-oxospiro[chroman-2,4′-piperidine]-6-carboxamide hydrochloride (389 mg), 1-cyclopropyl-4-ethoxy-1H-indole-6-carboxylic acid (245 mg), WSC hydrochloride (230 mg), HOBT (183 mg) and triethylamine (0.209 mL) were suspended in DMF (8 mL), and the mixture was stirred at 80° C. for 1.5 hours. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, and washed successively with water, 1 N hydrochloric acid, aqueous saturated sodium bicarbonate and saturated saline water. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified through silica gel column chromatography (chloroform/methanol) to afford the title compound as a colorless amorphous substance. 1H-NMR (400 MHz, DMSO-d6) δ: 8.78-8.71 (1H, m), 8.32-8.30 (1H, m), 8.08 (1H, dd, J=8.7, 2.3 Hz), 7.34 (1H, s), 7.28 (1H, d, J=3.4 Hz), 7.22-7.16 (2H, m), 6.99 (1H, s), 6.56 (1H, s), 6.38 (1H, d, J=3.4 Hz), 4.27-4.15 (1H, br m), 4.15 (2H, q, J=7.0 Hz), 3.77 (2H, d, J=5.9 Hz), 3.46-3.25 (3H, br m), 3.45-3.39 (1H, m), 2.95 (2H, s), 2.09-1.75 (4H, br m), 1.38 (3H, t, J=7.0 Hz), 1.08-1.01 (2H, m), 0.95-0.90 (2H, m); MS [M+H]+=545.

Workup

  1. temperatureto cool to room temperature
  2. washwashed successively with water, 1 N hydrochloric acid, aqueous saturated sodium bicarbonate and saturated saline water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified through silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-9c9af382fb114fb6923c64ca25900856
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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