4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochloride → 5-Bromo-2-{4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]anilino}-4-(4-methoxyphenoxy)pyrimidine

HRID 49797Notes

Reaction equation

HRID 49797 reaction equation
[Br:1][C:2]1[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[N:4][C:5](Cl)=[N:6][CH:7]=1.Cl.[OH:19][CH:20]([CH2:30][N:31]([CH3:33])[CH3:32])[CH2:21][O:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[N:4][C:5]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([O:22][CH2:21][CH:20]([OH:19])[CH2:30][N:31]([CH3:32])[CH3:33])=[CH:24][CH:25]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 227319204-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochlorideHCID 729424805-Bromo-2-chloro-4-(4-methoxyphenoxy)pyrimidine

Product 1

HCID 101633555-Bromo-2-{4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]anilino}-4-(4-methoxyphenoxy)pyrimidineYield 63.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 5-bromo-2-chloro-4-(4-methoxyphenoxy)pyrimidine (Method 1, 200 mg, 0.63 mmol) and 4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochloride (Method 8, 156 mg, 0.56 mmol) in NMP (4 ml) was heated at 100° C. for 6 hours. Silica (1 g) was added and volatile material was removed by evaporation. The residue was purified by column chromatography, eluting with 0-10% 2.0M methanolic ammonia solution in DCM, to give the product as a colourless solid (173 mg, 56%). MS (MH+): 489, 491; HPLC (RT): 4.68.

Workup

  1. additionSilica (1 g) was added
  2. customvolatile material was removed by evaporation
  3. customThe residue was purified by column chromatography
  4. washeluting with 0-10% 2.0M methanolic ammonia solution in DCM

Sources & evidence

ORD record
ord-b7563bb0b1e84c08bb04add1339df25d
Source dataset
uspto-grants-2004_03
Patent number
US06710052B2

Reaction notes

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