Water → 1,4-Dihydro-4-[3-[[2-[[3-[4-(3-methoxyphenyl)-1-piperidinyl]propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]phenyl]-2,3-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

HRID 2302321Notes

Reaction equation

HRID 2302321 reaction equation
C(O[C:4]1[C:7](=[O:8])[C:6](=[O:9])[C:5]=1[NH:10][C:11]1[CH:12]=[C:13]([CH:17]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH3:27])[NH:20][C:19](C)=[C:18]2[C:29]([O:31][CH3:32])=[O:30])[CH:14]=[CH:15][CH:16]=1)C.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:41]2[CH2:46][CH2:45][N:44]([CH2:47][CH2:48][CH2:49][NH2:50])[CH2:43][CH2:42]2)[CH:38]=[CH:39][CH:40]=1.O.[CH3:52]N(C=O)C>>[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:41]2[CH2:46][CH2:45][N:44]([CH2:47][CH2:48][CH2:49][NH:50][C:4]3[C:7](=[O:8])[C:6](=[O:9])[C:5]=3[NH:10][C:11]3[CH:12]=[C:13]([CH:17]4[C:18]([C:29]([O:31][CH3:32])=[O:30])=[CH:19][NH:20][CH:21]([CH3:27])[C:22]4([CH3:52])[C:23]([O:25][CH3:26])=[O:24])[CH:14]=[CH:15][CH:16]=3)[CH2:43][CH2:42]2)[CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 120432914-(3-Methoxyphenyl)piperidine-1-propanamineHCID 120438584-[3-[(2-Ethoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Product 1

HCID 1317234271,4-Dihydro-4-[3-[[2-[[3-[4-(3-methoxyphenyl)-1-piperidinyl]propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]phenyl]-2,3-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Procedure

The compound of Example 1 (54.7 mg, 0.124 mmol) and 4-(3-methoxyphenyl)piperidine-1-propanamine (41 mg, 0.165 mmol) were heated together in 2 mL DMF at 100° C. for 16 hours. Water was added into this crude reaction mixture after it was cooled to room temperature and the organic material was extracted with ethyl acetate (3×15 mL). Thin layer chromatography on SiO2 eluted with 10% methanol in methylene chloride showed essentially one single spot. This material was allowed to pass through a short bed of silica gel (Merck Type-H) and the pure product was, recovered as a foam after removal of solvents (43 mg, 54.0%). 1H NMR (DMSO-d6) δ 9.86 (br. s, 1H), 8.93 (br. s, 1H), 7.95 (br. s, 1H), 7.30 (d, 1H, J=7.7 Hz), 7.16 (m, 4H), 6.79 (m, 4H), 4.88 (s, 1H), 3.72 (s, 3H), 3.65 (m, 2H), 3.55 (s, 6H), 3.06 (m, 2H), 2.5 (m, 2H), 2.26 (s, 6H), 1.8 (m, 8H), 13C NMR (DMSO-d6) δ 167.38, 159.31, 145.95, 138.97, 129.36, 118.78, 112.45, 101.08, 54.87, 50.67, 18.28. Anal Calcd. for C36H42N4O7•2.10 H2O: C, 63.53; H, 6.84; N, 8.23. Found: C, 63.48; H, 6.85; N, 8.58.

Workup

  1. customreaction mixture after it
  2. extractionthe organic material was extracted with ethyl acetate (3×15 mL)
  3. washThin layer chromatography on SiO2 eluted with 10% methanol in methylene chloride
  4. customrecovered as a foam
  5. customafter removal of solvents (43 mg, 54.0%)

Sources & evidence

ORD record
ord-145353e4eb904f68baac4b9d2e2498c7
Source dataset
uspto-grants-2002_08
Patent number
US06432960B1

Reaction notes

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