Hydrochloric Acid → 5-{1'-[(1-Cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinic acid

HRID 420123Notes

Reaction equation

HRID 420123 reaction equation
C(N(CC)CC)C.[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([OH:22])=O)[CH:18]=3)[CH:13]=[CH:12]2)[CH2:10][CH2:9]1.Cl.[O:26]=[C:27]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39]([C:42]3[CH:43]=[N:44][CH:45]=[C:46]([CH:50]=3)[C:47]([OH:49])=[O:48])[CH:40]=2)[O:35][C:29]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28]1.Cl>CN(C=O)C.O>[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([N:32]4[CH2:33][CH2:34][C:29]5([CH2:28][C:27](=[O:26])[C:41]6[C:36](=[CH:37][CH:38]=[C:39]([C:42]7[CH:43]=[N:44][CH:45]=[C:46]([CH:50]=7)[C:47]([OH:49])=[O:48])[CH:40]=6)[O:35]5)[CH2:30][CH2:31]4)=[O:22])[CH:18]=3)[CH:13]=[CH:12]2)[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 666494031-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acidHCID 666494165-(4-Oxo-spiro[chroman-2,4'-piperidin]-6-yl)nicotinic acid hydrochloride

Product 1

HCID 249636015-{1'-[(1-Cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

N,N′-carbonyldiimidazole (130 mg) and triethylamine (0.446 mL) were added to a solution of 1-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acid (185 mg) in DMF (4 mL), and stirred at 70° C. for 20 hours. To the reaction mixture was added 5-(4-oxo-spiro[chroman-2,4′-piperidin]-6-yl)nicotinic acid hydrochloride (370 mg), which was further stirred at that temperature for 6 hours. 1 N hydrochloric acid and water were added to the reaction mixture, and the formed solid was collected by filtration. The solid was purified through silica gel column chromatography (chloroform/methanol) to obtain the intended compound. 1H-NMR (400 MHz, DMSO-d6) δ: 9.04-9.00 (2H, m), 8.40 (1H, s), 8.06-8.00 (2H, m), 7.30-7.22 (3H, m), 6.58 (1H, s), 6.40 (1H, d, J=3.2 Hz), 4.47-4.01 (1H, m), 3.88 (3H, s), 3.79-3.09 (4H, m), 2.96 (2H, s), 2.15-1.71 (4H, m), 1.09-1.01 (2H, m), 0.96-0.89 (2H, m); MS [M+H]+=552.

Workup

  1. stirringwas further stirred at that temperature for 6 hours
  2. filtrationthe formed solid was collected by filtration
  3. customThe solid was purified through silica gel column chromatography (chloroform/methanol)
  4. customto obtain the intended compound

Sources & evidence

ORD record
ord-e775c3ffb61641a8a2b27a09b35f161f
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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