1-Butanol → 4-Anilino-5-bromo-2-[4-(carboxyethyl)anilino]pyrimidine

HRID 480019Notes

Reaction equation

HRID 480019 reaction equation
[NH:1]([C:8]1[C:13]([Br: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.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24](O)=O)=[CH:19][CH:18]=1.Cl.[OH-:28].[Na+].[CH2:30]([OH:34])CCC>>[NH:1]([C:8]1[C:13]([Br:14])=[CH:12][N:11]=[C:10]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][C:30]([OH:34])=[O:28])=[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 5

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 145334-Aminophenylacetic acidHCID 14798Sodium HydroxideHCID 114033895-bromo-2-chloro-N-phenylpyrimidin-4-amine

Product 1

HCID 700292784-Anilino-5-bromo-2-[4-(carboxyethyl)anilino]pyrimidine

Conditions

Temperature
100 °C

Procedure

A mixture of 4-anilino-5-bromo-2-chloropyrimidine (Method 15; 1.50 g, 5.3 mmol), 4-aminophenylacetic acid (0.76 g, 5.0 mmol) and concentrated hydrochloric acid (0.98 ml, 5.3 mmol) in n-butanol (20 ml) was heated at 100° C. for 18 hours. The solid which separated out on cooling was collected by filtration and washed with n-butanol (20 ml) and diethyl ether (20 ml). The solid was dissolved in THF (20 ml) and methanol (10 ml). 2M Sodium hydroxide (3.80 ml, 7.6 mmol) was added and the solution was stirred for 18 hours. Volatile material was removed by evaporation and the residue was partitioned between ether (20 ml) and water (20 ml). The aqueous phase was separated and acidified to pH 3 to give the product as a white solid (350 mg). NMR: 7.0 (d, 2H), 7.2 (m, 1H), 7.4 (m, 2H), 7.5 (d, 2H), 7.6 (d, 2H), 8.2 (s, 1H), 8.6 (s, 1H), 9.3 (s, 1H); MS (MH+); 399, 401.

Workup

  1. customThe solid which separated out
  2. temperatureon cooling
  3. filtrationwas collected by filtration
  4. washwashed with n-butanol (20 ml) and diethyl ether (20 ml)
  5. dissolutionThe solid was dissolved in THF (20 ml)
  6. customVolatile material was removed by evaporation
  7. customthe residue was partitioned between ether (20 ml) and water (20 ml)
  8. customThe aqueous phase was separated

Sources & evidence

ORD record
ord-4be28eff1c904cd8838ffb366d8d111d
Source dataset
uspto-grants-2003_11
Patent number
US06649608B2

Reaction notes

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