Hydrochloric Acid → N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 2093810Notes

Reaction equation

HRID 2093810 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[NH:11][N:10]=2)[C:5]([Cl:15])=[CH:4][N:3]=1.[Br:16][C:17]1[C:23]([CH3:24])=[CH:22][C:20]([NH2:21])=[C:19]([CH3:25])[CH:18]=1.Cl>C(O)(C)C.CCOC(C)=O>[Br:16][C:17]1[C:23]([CH3:24])=[CH:22][C:20]([NH:21][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:13]=[C:12]([CH3:14])[NH:11][N:10]=3)[C:5]([Cl:15])=[CH:4][N:3]=2)=[C:19]([CH3:25])[CH:18]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 81671304-Bromo-2,5-dimethylanilineHCID 114022722,5-Dichloro-N-(5-methyl-1H-pyrazol-3-yl)-4-pyrimidinamine2×

Product 1

HCID 86653324N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (732 mg, 3 mmol), 4-bromo-2,5-dimethylaniline (554 mg, 2 mmol) and conc. aqueous HCl (1.5 mL) in iso-propanol (15 mL) was heated in a microwave for 40 min at 130° C. LCMS showed that the reaction was not complete, and additional 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (732 mg, 3 mmol) was added to the reaction. The reaction was again heated in a microwave for an additional 60 min at 130° C. The crude reaction mixture was then diluted with EtOAc (100 mL), sequentially washed with saturated aqueous NaHCO3 (2×20 mL) and brine (10 mL), dried over Na2CO3 and concentrated in vacuo. The crude product was purified by silica chromatography (0-10% MeOH in EtOAc gradient with 1% NH3 additive) to give N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as an off-white solid; ESMS m/z 407.2 (M+H+).

Workup

  1. temperatureThe reaction was again heated in a microwave for an additional 60 min at 130° C
  2. customThe crude reaction mixture
  3. washsequentially washed with saturated aqueous NaHCO3 (2×20 mL) and brine (10 mL)
  4. dry with materialdried over Na2CO3
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica chromatography (0-10% MeOH in EtOAc gradient with 1% NH3 additive)

Sources & evidence

ORD record
ord-2520bbdda37e446f97a78fe6e863e3e6
Source dataset
uspto-grants-2013_05
Patent number
US08445505B2

Reaction notes

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