Diisopropylethylamine → 6-Chloro-N4-(5-isopropyl-1H-pyrazol-3-yl)-N2-(3-phenylisoxazol-5-ylmethyl)-pyrimidine-2,4-diamine

HRID 1510400Notes

Reaction equation

HRID 1510400 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[NH:11][N:10]=2)[CH:5]=[C:4]([Cl:17])[N:3]=1.C(N(C(C)C)CC)(C)C.[C:27]1([C:33]2[CH:37]=[C:36]([CH2:38][NH2:39])[O:35][N:34]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(O)CCC>[Cl:17][C:4]1[N:3]=[C:2]([NH:39][CH2:38][C:36]2[O:35][N:34]=[C:33]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:37]=2)[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[NH:11][N:10]=2)[CH:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27641651-(3-Phenyl-1,2-oxazol-5-yl)methanamineHCID 578664512,6-Dichloropyrimidin-4-yl-(5-isopropyl-1H-pyrazol-3-yl)-amine

Product 1

HCID 578664486-Chloro-N4-(5-isopropyl-1H-pyrazol-3-yl)-N2-(3-phenylisoxazol-5-ylmethyl)-pyrimidine-2,4-diamineYield 45%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2,6-dichloropyrimidin-4-yl-(5-isopropyl-1H-pyrazol-3-yl)-amine (19.44 g, 71.7 mmol) in 1-butanol (200 mL) was added diisopropylethylamine (23.7 mL, 143 mmol) and 3-phenylisoxazol-5-ylmethylamine (15.0 g, 86.1 mmol). The mixture was stirred at 90° C. for 30 h, then concentrated on a rotary evaporator. The residue was taken up in 100 mL of methanol and boiled until the volume reached around 50 mL. The solution was allowed to cool to room temperature and then placed in the refrigerator overnight. The solid that formed was collected by filtration, while the filtrate was concentrated on a rotary evaporator, heated to boiling in methanol and cooled overnight in the refrigerator. This solid was collected and the filtrate was subjected to methanol recrystallization a third time. The three solids were combined to give the desired product (13.1 g, 45%) as a white solid.

Workup

  1. concentrationconcentrated on a rotary evaporator
  2. temperatureto cool to room temperature
  3. customplaced in the refrigerator overnight
  4. customThe solid that formed
  5. filtrationwas collected by filtration, while the filtrate
  6. concentrationwas concentrated on a rotary evaporator
  7. temperatureheated
  8. temperaturecooled overnight in the refrigerator
  9. customThis solid was collected
  10. customthe filtrate was subjected to methanol recrystallization a third time

Sources & evidence

ORD record
ord-c52ad996a9ba4a1d8a6b42a7d8c0089b
Source dataset
uspto-grants-2012_07
Patent number
US08211929B2

Reaction notes

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