Hydrochloric Acid → HCID 18186493, compound

HRID 1357522Notes

Reaction equation

HRID 1357522 reaction equation
[NH:1]([C:8]1[C:13]([CH2:14][O:15][CH2:16][CH3:17])=[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.OC1[CH:38]=[C:37](C)[O:36][N:35]=1.Cl>CN1C(=O)CCC1>[NH:1]([C:8]1[C:13]([CH2:14][O:15][C:16]2[CH:17]=[C:37]([CH3:38])[O:36][N:35]=2)=[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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24781HymexazolHCID 11774967HCID 11774967, compound

Product 1

HCID 18186493HCID 18186493, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

4-Anilino-5-(ethoxymethyl)-2-{4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]anilino}pyrimidine (Example 86, 100 mg, 0.23 mmol) was dissolved in NMP (2 ml). 3-Hydroxy-5-methylisoxazole (45 mg, 0.46 mmol) and ethereal hydrogen chloride (1.0M; 0.46 ml, 0.46 mmol) were added, and the solution was heated at 100° C. for 20 hours. Volatile material was removed by evaporation, and the residue 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 (49 mg, 44%). NMR: 2.17 (s, 6H), 2.22 (s, 3H), 2.2-2.45 (m, 2H), 3.75-3.9 (m, 3H), 4.73 (br s, 1H), 4.49 (s, 2H), 5.78 (s, 1H), 6.80 (d, 2H), 7.02 (t, 1H), 7.30 (dd, 2H), 7.50 (d, 2H), 7.70 (d, 2H) 8.04 (s, 1H), 8.76 (s, 1H), 9.05 (s, 1H); MS (MH+): 491.5.

Workup

  1. customVolatile material was removed by evaporation
  2. dissolutionthe residue 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-b45d425066d8419f80f55439bc7913e8
Source dataset
uspto-grants-2003_07
Patent number
US06593326B1

Reaction notes

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