Hydrochloric Acid → HCID 18186462, compound

HRID 1357524Notes

Reaction equation

HRID 1357524 reaction equation
[NH:1]([C:8]1[C:13]([CH2:14]OCC)=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH:27]([OH:32])[CH2:28][N:29]([CH3:31])[CH3:30])=[CH:21][CH:20]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:33][C:34]([NH2:36])=[O:35].Cl.C(OCC)C>O1CCOCC1>[NH:1]([C:8]1[C:13]([CH2:14][NH:33][C:34]([NH2:36])=[O:35])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH:27]([OH:32])[CH2:28][N:29]([CH3:31])[CH3:30])=[CH:23][CH:24]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 3283Diethyl EtherHCID 11774967HCID 11774967, compound

Product 1

HCID 18186462HCID 18186462, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Anilino-5-(ethoxymethyl)-2-{4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]anilino}pyrimidine (Example 86, 70 mg, 0.16 mmol) was dissolved in 1,4-dioxane (2 ml). Urea (12 mg, 0.19 mmol) and ethereal hydrogen chloride (1.0M; 0.19 ml, 0.19 mmol) were added, and the suspension was heated at 100° C. for 20 hours. Diethyl ether (20 ml) was added, and the precipitated solid collected by filtration. The solid was dissolved in 10% methanol solution in DCM (3 ml), and loaded on a Varian Mega Bond Elut column. The column was eluted with 0-2.5% methanol solution in DCM containing 0.5% aqueous ammonia solution. Concentration of the appropriate fractions and trituration of the residue with diethyl ether gave the product as a white crystalline solid (20 mg, 28%). NMR: 2.18 (s, 6H), 2.2-2.45 (m, 2H), 3.75-3.9 (m, 3H), 4.07 (d, 2H), 4.74 (br d, 1H), 5.85 (s, 2H), 6.62 (t, 1H), 6.80 (d, 2H), 6.98 (t, 1H), 7.27 (dd, 2H), 7.54 (d, 2H), 7.77 (d, 2H), 7.88 (s, 1H), 8.88 (s, 1H), 9.88 (s, 1H); MS (MH+): 452.4.

Workup

  1. filtrationthe precipitated solid collected by filtration
  2. dissolutionThe solid was dissolved in 10% methanol solution in DCM (3 ml)
  3. washThe column was eluted with 0-2.5% methanol solution in DCM containing 0.5% aqueous ammonia solution

Sources & evidence

ORD record
ord-c51991294f14426186022d3aece4aabe
Source dataset
uspto-grants-2003_07
Patent number
US06593326B1

Reaction notes

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