Dimethylformamide → 4-[3-[[2-[[3-(4-cyclohexyl-1-piperazinyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]-4-fluorophenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

HRID 2302324Notes

Reaction equation

HRID 2302324 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][N:35]([CH:37]=O)[CH3:36]>>[CH:34]1([N:35]2[CH2:37][CH2:36][N:35]([CH2:37][CH2:4][CH2:5][NH:10][C:4]3[C:7](=[O:8])[C:6](=[O:9])[C:5]=3[NH:10][C:11]3[CH:12]=[C:13]([CH:18]4[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:28])[NH:21][C:20]([CH3:29])=[C:19]4[C:30]([O:32][CH3:33])=[O:31])[CH:14]=[CH:15][C:16]=3[F:17])[CH2:34][CH2:36]2)[CH2:13][CH2:12][CH2:11][CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 6228DimethylformamideHCID 120432874-[3-[(2-Ethoxy-3,4-dioxo-1cyclobuten-1-yl)amino]-4-fluorophenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Product 1

HCID 120432894-[3-[[2-[[3-(4-cyclohexyl-1-piperazinyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]-4-fluorophenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Procedure

The compound of Example 2 (147 mg, 0.321 mmol) and 4-cyclohexyl-1-piperazine-1-propanamine (72 mg, 0.320 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 (158 mg, 77.5%): mp 229-230° C.; 1H NMR (DMSO-d6) δ 9.37 (br. s, 1H), 8.96 (br. s, 1H), 8.03 (br. 1H), 7.79 (d, 1H, J=7.6 Hz), 7.59 (dd, 1H, J=8.98, 5.21 Hz), 7.07 (dd, 1H, J=8.46, 11.37 Hz), 6.2 (m, 1H), 4.84 (s, 1H), 3.62-3.60 (m, 2H), 3.54 (s, 6H), 2.45 (m, 5H), 2.33-2.26 (m, 4H), 2.26 (s, 6H), 1.70-1.68 (m, 7H), 1.59-1.52 (br. 1H), 1.18-1.04 (m, 6H), 13C NMR (DMSO-d6) δ 179.63, 169.50, 167.31, 146.22, 129.07, 126.75, 125.98, 122.13, 119.68, 100.93, 62.55, 54.87, 50.60, 48.22, 42.13, 28.20, 27.62, 25.86, 25.57, 25.21, 18.31. Anal Calcd. for C34H44FN5O6•0.05 H2O: C, 63.94; H, 6.96; N, 10.97. Found: C, 63.95; H, 6.94; N, 10.74.

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 (158 mg, 77.5%)

Sources & evidence

ORD record
ord-7b9d03fe8d724511a291ae20c0d7b995
Source dataset
uspto-grants-2002_08
Patent number
US06432960B1

Reaction notes

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