Acetic Acid → HCID 67171992, compound

HRID 545170Notes

Reaction equation

HRID 545170 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([C:15]([N:17]2[CH2:22][CH2:21][C:20]3([CH2:31][C:30](=[O:32])[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([S:33]([NH2:36])(=[O:35])=[O:34])[CH:28]=4)[O:23]3)[CH2:19][CH2:18]2)=[O:16])[CH:4]=1.CCN=C=NCCCN(C)C.[CH3:48][C:49](O)=[O:50].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CN(C1C=CN=CC=1)C>[C:49]([NH:36][S:33]([C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][CH:26]=1)[O:23][C:20]1([CH2:19][CH2:18][N:17]([C:15]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:12]4[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=4)[N:6]=3)=[O:16])[CH2:22][CH2:21]1)[CH2:31][C:30]2=[O:32])(=[O:34])=[O:35])(=[O:50])[CH3:48]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516892Sodium BicarbonateHCID 16041745HCID 16041745, compound

Product 1

HCID 67171992HCID 67171992, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Procedure

293 mg of 1′-[(4,8-Dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide was dissolved in 5 mL of CHCl3, and 10.7 mg of DMAP and 120 mg of EDCI were added to it, and then 0.036 mL of AcOH was added thereto and the mixture was stirred overnight at room temperature. Aqueous saturated sodium hydrogen carbonate was added to the reaction solution, and then extracted three times with ethyl acetate, and the organic layer was washed successively with aqueous saturated sodium hydrogencarbonate solution, water and saturated brine. The aqueous layers were combined, hydrochloric acid was added to it to thereby make it have a pH of 7.5, and this was then extracted with CHCl3. The extract was dried over sodium sulfate and concentrated, and the resulting residue was purified through silica gel column chromatography (CHCl3, 4.5% MeOH/CHCl3) to obtain 317 mg of N-acetyl-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide. 26.3 mg of the product was dissolved in 1.5 mL of THF, and 15.0 mg of PPh3, 0.011 mL of DIAD and 2.7 mL of MeOH were added to it and the mixture was stirred at room temperature for one day. The reaction solution was concentrated and purified through silica gel thin-layer chromatography (n-Hexane/EtOAc=1/5) to obtain 26.3 mg of N-acetyl-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-N-methyl-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide as a colorless foam substance. This was dissolved in 0.8 mL of MeOH and 0.1 mL of water, added by 0.1 mL of saturated sodium hydrogen carbonate solution, and then stirred for 2 hours. The reaction solution was diluted with water and extracted with CHCl3. The organic layer was dried over sodium sulfate, and concentrated, and the residue was purified through silica gel thin-layer chromatography (CHCl3/MeOH=18/1) to obtain the intended compound as a colorless foam substance. 1H-NMR (300 MHz, CDCl3) δ: 8.40-8.38 (1H, m), 8.01-7.97 (1H, m), 7.80-7.74 (1H, m), 7.51-7.43 (1H, m), 7.20 (1H, s), 7.17-7.13 (1H, m), 7.11-7.06 (1H, m), 4.67-4.58 (2H, m), 4.28-4.18 (1H, m), 4.09 (3H, s), 4.03 (3H, s), 3.67-3.56 (1H, m), 3.44-3.33 (1H, m), 2.92-2.78 (2H, m), 2.68 (3H, d, J=5.4 Hz), 2.28-2.17 (1H, m), 2.13-1.88 (3H, m). MS [M+H]+=526.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washthe organic layer was washed successively with aqueous saturated sodium hydrogencarbonate solution, water and saturated brine
  3. additionhydrochloric acid was added to it
  4. extractionthis was then extracted with CHCl3
  5. dry with materialThe extract was dried over sodium sulfate
  6. concentrationconcentrated
  7. customthe resulting residue was purified through silica gel column chromatography (CHCl3, 4.5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-fa86fc6fa07d44a68573134f78d97f7b
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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