Dimethylformamide dimethyl acetal → HCID 15407402, compound

HRID 1871083Notes

Reaction equation

HRID 1871083 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:16]([C:17](=O)[CH3:18])=[C:15]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:14]=[CH:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:27]OC(OC)N(C)C.[CH3:35][NH:36][C:37]([NH2:39])=[NH:38].CC[O-].[Na+]>C(O)CC.O.Cl>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][CH:9]([N:12]2[C:16]([C:17]3[CH:18]=[CH:35][N:36]=[C:37]([NH:39][CH3:27])[N:38]=3)=[C:15]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:14]=[CH:13]2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 78373Dimethylformamide dimethyl acetalHCID 2723922Sodium ethoxideHCID 99507171-(1-Ethoxycarbonyl-4-piperidinyl)-4-(4-fluorophenyl)-5-acetylimidazoleHCID 178485088HCID 178485088, compound

Product 1

HCID 15407402HCID 15407402, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the ketoimidazole prepared in Example 2 above (2.1 g, 5.85 mmol) in 10.5 mL of 1-propanol was added N,N-dimethylformamide dimethyl acetal (1.32 mL, 1.18 g, 9.94 mmol) and the solution was heated at 100° C. for 6 h. At this time, TLC indicated no starting material and N-methylguanidine.HCl (0.96 g, 8.77 mmol) and NaOEt (21% w/w solution, 3.50 mL, 3.05 g, 9.35 mmol) were added. After 18 hours, the solution was cooled to room temperature, diluted with 40 mL of water, 50 mL of 3N HCl and 50 mL of EtOAC. The layers were separated and the organic layer wash washed again with 20 mL of 3N HCl. The combined aqueous layers were basified with solid K2CO3 until bubbling ceased. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organics were washed with 3×100 mL of water, concentrated and the residue was recrystallized from EtOAc to give 1.24 g (50%) of the title compound: mp=205-206° C.; IR (KBr) 3242, 3110, 1695, 1588, 1568, 1532, 1507 cm-1 ; 1H NMR (CDCl3) δ 8.15 (1H, d, J=5.0 Hz), 7.71 (1H, s), 7.44 (2H, m), 6.97 (2H, t, J=8.7 Hz), 6.40 (1H, d, J=5.0 Hz), 5.18 (1H, m), 4.83 (1H, m), 4.34 (2H, m), 4.15 (2H, q, J=7.1 Hz), 3.02 (3H, d, J=5.0 Hz), 2.81 (2H, m), 2.19 (2H, m), 1.87 (2H, dq, J=4.4, 12.5 Hz), 1.27 (3H, t, J=7.1 Hz); 13C NMR (CDCl3) δ 164.00, 163.03, 160.73, 158.51, 158.32, 155.31, 141.96, 135.57, 130.52, 130.07, 129.97, 125.01, 115.39, 115.11, 111.73, 61.61, 53.80, 43.42, 33.43, 28.43, 14.63; Anal. Cald for C22H25N6O2F; C, 62.2; H, 5.9; N, 19.8; Found C, 61.9, H, 6.0; N, 19.4.

Workup

  1. temperaturethe solution was cooled to room temperature
  2. customThe layers were separated
  3. washthe organic layer wash
  4. washwashed again with 20 mL of 3N HCl
  5. customuntil bubbling
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. washThe combined organics were washed with 3×100 mL of water
  8. concentrationconcentrated
  9. customthe residue was recrystallized from EtOAc

Sources & evidence

ORD record
ord-e9e744ba4b5d47fbb7d59794177b9260
Source dataset
uspto-grants-2000_08
Patent number
US06100399

Reaction notes

Loading…