Hydrochloric Acid → 5-(1'-{[2,6-Dimethoxybiphenyl-4-yl]carbonyl}-4-oxospiro[chroman-2,4'-piperidin]-6-yl)pyridine-3-carboxylic acid

HRID 1096897Notes

Reaction equation

HRID 1096897 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]1[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[C:17]([O:24][CH3:25])[C:16]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl.Cl.[O:34]=[C:35]1[C:49]2[C:44](=[CH:45][CH:46]=[C:47]([C:50]3[CH:51]=[C:52]([C:56]([OH:58])=[O:57])[CH:53]=[N:54][CH:55]=3)[CH:48]=2)[O:43][C:37]2([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36]1.Cl>O.C(N(CC)CC)C.CN(C=O)C>[CH3:25][O:24][C:17]1[CH:18]=[C:19]([C:21]([N:40]2[CH2:41][CH2:42][C:37]3([CH2:36][C:35](=[O:34])[C:49]4[C:44](=[CH:45][CH:46]=[C:47]([C:50]5[CH:51]=[C:52]([C:56]([OH:58])=[O:57])[CH:53]=[N:54][CH:55]=5)[CH:48]=4)[O:43]3)[CH2:38][CH2:39]2)=[O:23])[CH:20]=[C:15]([O:14][CH3:13])[C:16]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 167685332,6-Dimethoxybiphenyl-4-carboxylic acidHCID 666494905-{4-Oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinic acid di-hydrochloride

Product 1

HCID 249996265-(1'-{[2,6-Dimethoxybiphenyl-4-yl]carbonyl}-4-oxospiro[chroman-2,4'-piperidin]-6-yl)pyridine-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

Carbonyldiimidazole (81 mg) was added to a DMF solution (2 mL) of 2,6-dimethoxybiphenyl-4-carboxylic acid (129 mg), and stirred at 60° C. for 2.5 hours. To the reaction liquid, added were 5-(4-oxospiro[chroman-2,4′-piperidin]-6-yl)pyridine-3-carboxylic acid dihydrochloride (246 mg) and triethylamine (209 ml), and stirred at that temperature for 17 hours. 1 N hydrochloric acid and water were added to the reaction liquid, and the resulting solid was purified through high-performance preparative liquid chromatography (0.1% TFA, water/acetonitrile). Then, this was further purified through silica gel thin-layer chromatography (chloroform/methanol) to obtain the title compound. 1H-NMR (400 MHz, DMSO-d6) δ: 9.06 (1.0H, d, J=2.4 Hz), 9.02 (1.0H, d, J=2.0 Hz), 8.41 (1.0H, dd, J=2.4, 2.0 Hz), 8.12-8.01 (2.0H, m), 7.38-7.32 (2.0H, m), 7.29-7.24 (2.0H, m), 7.23-7.19 (2.0H, m), 6.75 (2.0H, s), 4.36-4.22 (1.0H, br m), 3.69-3.12 (3.0H, m), 3.68 (6.0H, s), 2.95 (2.0H, s), 2.15-1.93 (2.0H, m), 1.91-1.75 (2.0H, m). MS [M+H]+=579.

Workup

  1. customTo the reaction liquid
  2. additionadded
  3. stirringstirred at that temperature for 17 hours
  4. customthe resulting solid was purified through high-performance preparative liquid chromatography (0.1% TFA, water/acetonitrile)
  5. customThen, this was further purified through silica gel thin-layer chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-d6b5786f34044b8487520253438c6db9
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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