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

HRID 2302323Notes

Reaction equation

HRID 2302323 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]([CH3:28])=[C:18]2[C:29]([O:31][CH3:32])=[O:30])[CH:14]=[CH:15][CH:16]=1)C.[CH3:33][N:34]([CH:36]=O)[CH3:35]>>[CH:33]1([N:34]2[CH2:36][CH2:35][N:34]([CH2:36][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:17]4[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH3:27])[NH:20][C:19]([CH3:28])=[C:18]4[C:29]([O:31][CH3:32])=[O:30])[CH:14]=[CH:15][CH:16]=3)[CH2:33][CH2:35]2)[CH2:13][CH2:12][CH2:11][CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 6228DimethylformamideHCID 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 120432884-[3-[[2-[[3-(4-cyclohexyl-1-piperazinyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, Dimethyl Ester

Procedure

The compound of Example 1 (160 mg, 0.364 mmol) and 4-cyclohexyl-1-piperazine-1-propanamine (81.4 mg, 0.362 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 (165 mg, 73.6%): mp 210-212° C.; 1H NMR (DMSO-d6) δ 9.52 (br. s, 1H), 8.91 (br. s, 1H), 7.54 (br. 1H), 7.27 (d, 1H, J=7.3 Hz), 7.16 (m, 2H), 6.80 (d, 1H, J=7.5 Hz), 4.88 (s, 1H), 3.61 (m, 2H), 3.55 (s, 6H), 2.45 (m, 5H), 2.30 (m, 4H), 2.26 (s, 6H), 1.69 (m, 7H), 1.53 (br. d, 1H, J=11.0 Hz), 1.11 (m, 6H); 13C NMR (DMSO-d6) δ 207.50, 207.28, 206.89, 203.73, 199.89, 194.77, 193.47, 192.12, 169.21, 167.38, 163.58, 153.67, 149.15, 145.92, 138.90, 128.87, 121.51, 116.60, 115.86, 101.11, 62.50, 54.94, 53.29, 50.57, 49.90, 48.28, 42.22, 28.32, 27.73, 26.26, 23.50, 18.29, 17.37. Anal Calcd. for C34H45N5O6•0.13 H2O: C, 65.64; H, 7.33; N, 11.26. Found: C, 65.65; H, 7.25; N, 11.09.

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 (165 mg, 73.6%)

Sources & evidence

ORD record
ord-8ab2edfc4940489093d1e4c4e5ec76f6
Source dataset
uspto-grants-2002_08
Patent number
US06432960B1

Reaction notes

Loading…