4-[3-[(2-Ethoxy-3,4-dioxo-1cyclobuten-1-yl)amino]-4-fluorophenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester → 4-[4-Fluoro-3-[[2-[[3-[4-(3-methoxyphenyl)-1-piperidinyl]propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

HRID 2302322Notes

Reaction equation

HRID 2302322 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:18]2[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:28])[NH:21][C:20]([CH3:29])=[C:19]2[C:30]([O:32][CH3:33])=[O:31])[CH:14]=[CH:15][C:16]=1[F:17])C.[CH3:34][O:35][C:36]1[CH:37]=[C:38]([CH:42]2[CH2:47][CH2:46][N:45]([CH2:48][CH2:49][CH2:50][NH2:51])[CH2:44][CH2:43]2)[CH:39]=[CH:40][CH:41]=1>CN(C=O)C>[F:17][C:16]1[CH:15]=[CH:14][C:13]([CH:18]2[C:19]([C:30]([O:32][CH3:33])=[O:31])=[C:20]([CH3:29])[NH:21][C:22]([CH3:28])=[C:23]2[C:24]([O:26][CH3:27])=[O:25])=[CH:12][C:11]=1[NH:10][C:5]1[C:6](=[O:9])[C:7](=[O:8])[C:4]=1[NH:51][CH2:50][CH2:49][CH2:48][N:45]1[CH2:44][CH2:43][CH:42]([C:38]2[CH:39]=[CH:40][CH:41]=[C:36]([O:35][CH3:34])[CH:37]=2)[CH2:47][CH2:46]1

Participants

4

Reactant 2

HCID 120432874-[3-[(2-Ethoxy-3,4-dioxo-1cyclobuten-1-yl)amino]-4-fluorophenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl EsterHCID 120432914-(3-Methoxyphenyl)piperidine-1-propanamine

Product 1

HCID 102117734-[4-Fluoro-3-[[2-[[3-[4-(3-methoxyphenyl)-1-piperidinyl]propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound of Example 2 (98.3 mg, 0.215 mmol) and 4-(3-methoxyphenyl)piperidine-1-propanamine (64 mg, 0.258 mmol) were stirred in 2 mL DMF at room temperature for 64 hours. The crude reaction mixture was evaporated to dryness under high vacuum (0.1 mmHg) at 50-55° C. The resulting gum was triturated with methylene chloride followed by the addition of hexanes. The titled compound precipitated out as fine creamy white crystalline solid (120 mg, 84.6%): mp 205-207° C.; 1H NMR (DMSO-d6) δ 9.38 (br. s, 1H), 8.96 (br. s, 1H), 8.04 (br. t, 1H, J=3 Hz), 7.80 (d, 1H, J=7.2 Hz), 7.10 (m, 2H), 6.77 (m, 4H), 4.85 (s, 1H), 3.71 (s, 3H), 3.65 (q, 2H, J=6.0 Hz), 3.53 (s, 6H), 2.95 (d, 2H, J=10.5 Hz), 2.40 (m, 3H), 2.25 (s, 6H), 1.97 (m, 2H), 1.67.(m, 6H), 13C NMR (DMSO-d6) δ 184.94, 179.65, 169.52, 167.32, 163.03, 159.26, 147.95, 146.23, 145.07, 129.25, 126.76, 126.62, 119.68, 118.81, 114.66, 114.40, 112.41, 111.35, 100.93, 55.14, 54.83, 53.73, 50.60, 32.93, 27.84, 18.31. Anal Calcd. for C36H41 FN4O7•0.14 H2O: C, 65.19; H, 6.27; N, 8.45. Found: C, 65.20; H, 6.28; N, 8.37.

Workup

  1. customThe crude reaction mixture
  2. customwas evaporated to dryness under high vacuum (0.1 mmHg) at 50-55° C
  3. customThe resulting gum was triturated with methylene chloride
  4. additionfollowed by the addition of hexanes
  5. customThe titled compound precipitated out as fine creamy white crystalline solid (120 mg, 84.6%)

Sources & evidence

ORD record
ord-91b34dd5cc2440559db47f0b4bdce1f0
Source dataset
uspto-grants-2002_08
Patent number
US06432960B1

Reaction notes

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