1-Hydroxybenzotriazole → N-Carbamoylmethyl-1'-{[3,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl]carbonyl}-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide

HRID 1096894Notes

Reaction equation

HRID 1096894 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].[CH2:25]([O:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([O:43][CH2:44][CH3:45])[C:36]=1[C:37]1[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=1)[C:31](O)=[O:32])[CH3:26].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O.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:31]([C:30]3[CH:34]=[C:35]([O:43][CH2:44][CH3:45])[C:36]([C:37]4[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=4)=[C:28]([O:27][CH2:25][CH3:26])[CH:29]=3)=[O:32])[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 579310273,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)benzoic acidHCID 66649519N-Carbamoylmethyl-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide hydrochloride

Product 1

HCID 57930898N-Carbamoylmethyl-1'-{[3,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl]carbonyl}-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

N-Carbamoylmethyl-4-oxospiro[chroman-2,4′-piperidine]-6-carboxamide hydrochloride (354 mg), 3,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)benzoic acid (145 mg), WSC hydrochloride (115 mg), HOBT (91.2 mg) and triethylamine (0.209 mL) were suspended in DMF (3 mL), and stirred at 50° C. for 16 hours. Water was added to it, the formed solid was taken out through filtration, and the resulting solid was purified through silica gel column chromatography (chloroform/methanol), and crystallized from chloroform/diethyl ether to obtain the title compound. 1H-NMR (400 MHz, DMSO-d6) δ: 8.75 (1.0H, t, J=5.6 Hz), 8.35-8.28 (1.0H, m), 8.09 (1.0H, dd, J=8.8, 2.2 Hz), 8.04 (1.0H, s), 7.92 (1.0H, s), 7.35 (1.0H, s), 7.17 (1.0H, d, J=8.8 Hz), 7.00 (1.0H, s), 6.68 (2.0H, s), 4.31-4.02 (1.0H, m), 4.08 (4.0H, q, J=7.0 Hz), 3.86 (3.0H, s), 3.77 (2.0H, d, J=5.9 Hz), 3.64-3.02 (3.0H, m), 2.93 (2.0H, s), 2.10-1.72 (4.0H, m), 1.37 (6.0H, t, J=7.0 Hz). MS [M+H]+=590.

Workup

  1. filtrationthe formed solid was taken out through filtration
  2. customthe resulting solid was purified through silica gel column chromatography (chloroform/methanol)
  3. customcrystallized from chloroform/diethyl ether

Sources & evidence

ORD record
ord-af8ebcf91c69407d84580d2f9499537b
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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