Hydrochloric Acid → 4-Anilino-5-chloro-2-{4-[2-hydroxy-3-(isopropylamino)propoxy]anilino}pyrimidine

HRID 1357528Notes

Reaction equation

HRID 1357528 reaction equation
[NH:1]([C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10](Cl)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:16][CH:17]([CH2:27][NH:28][CH:29]([CH3:31])[CH3:30])[CH2:18][O:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1.Cl>C(O)CCC.CO>[NH:1]([C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([NH:24][C:23]2[CH:25]=[CH:26][C:20]([O:19][CH2:18][CH:17]([OH:16])[CH2:27][NH:28][CH:29]([CH3:30])[CH3:31])=[CH:21][CH:22]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168716DesacetylpractololHCID 187680474-Anilino-2,5-dichloropyrimidine

Product 1

HCID 181864964-Anilino-5-chloro-2-{4-[2-hydroxy-3-(isopropylamino)propoxy]anilino}pyrimidineYield 41.3%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

4-Anilino-2,5-dichloropyrimidine (Method 7, 241 ma, 1.0 mmol) was dissolved in n-butanol (20 ml) and methanol (4 ml). 4-[2-Hydroxy-3-(isopropylamino)propoxy]aniline (obtained as described in Pharmazie 1980, 35, 278; 202 mg, 0.9 mmol) and ethereal hydrogen chloride (1.0M; 2 ml, 2.0 mmol) were added and the solution was heated at 100° C. for 20 hours, allowed to cool to ambient temperature and then concentrated to a volume of 5 ml. The solution was loaded on a Varian Mega Bond Elut column and the column was eluted with 0-4% 2.0M methanolic ammonia solution in DCM. Concentration of the appropriate fractions and recrystallization of the residue from acetonitrile gave the product as a white solid (159 mg, 41%). NMR: 1.0 (d, 6H), 2.5-2.6 (m, 1H), 2.65-2.75 (m, 2H), 3.8-3.95 (m, 3H), 4.9 (br s, 1H), 6.8 (d, 2H), 7.1 (t, 1H), 7.35 (t, 2H), 7.45 (d, 2H), 7.65 (d, 2H), 8.1 (s, 1H), 8.7 (s, 1H), 9.1 (s, 1H); MS (MH+): 428, 430.

Workup

  1. temperatureto cool to ambient temperature
  2. concentrationconcentrated to a volume of 5 ml
  3. washthe column was eluted with 0-4% 2.0M methanolic ammonia solution in DCM
  4. customConcentration of the appropriate fractions and recrystallization of the residue from acetonitrile

Sources & evidence

ORD record
ord-b76d23bf1dc8424bb186f9f8de939258
Source dataset
uspto-grants-2003_07
Patent number
US06593326B1

Reaction notes

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