Phenyl isocyanate → 5-(3-(2-((tert-butyldimethylsilyl)oxy)ethyl)isoxazol-5-yl)-N2-(3-fluorophenyl)-N4-propylpyrimidine-2,4-diamine

HRID 2284796Notes

Reaction equation

HRID 2284796 reaction equation
[C:1]([C:3]1[C:4]([NH:17][CH2:18][CH2:19][CH3:20])=[N:5][C:6]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)=[N:7][CH:8]=1)#[CH:2].[C:21]([Si:25]([CH3:34])([CH3:33])[O:26][CH2:27][CH2:28][CH2:29][N+:30]([O-])=[O:31])([CH3:24])([CH3:23])[CH3:22].C1(N=C=O)C=CC=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Si:25]([O:26][CH2:27][CH2:28][C:29]1[CH:2]=[C:1]([C:3]2[C:4]([NH:17][CH2:18][CH2:19][CH3:20])=[N:5][C:6]([NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=3)=[N:7][CH:8]=2)[O:31][N:30]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:34])[CH3:33]

Participants

8

Reactant 4

HCID 7672Phenyl isocyanate2×HCID 8471Triethylamine2×HCID 13635020tert-Butyldimethyl(3-nitropropoxy)silaneHCID 900525125-ethynyl-N2-(3-fluorophenyl)-N4-propylpyrimidine-2,4-diamine

Product 1

HCID 1317335355-(3-(2-((tert-butyldimethylsilyl)oxy)ethyl)isoxazol-5-yl)-N2-(3-fluorophenyl)-N4-propylpyrimidine-2,4-diamineYield 42%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-ethynyl-N2-(3-fluorophenyl)-N4-propylpyrimidine-2,4-diamine (S2, 30 mg) and tert-butyldimethyl(3-nitropropyloxy)silane (S3, 146 mg) synthesized according to the method described in Journal of Medicinal Chemistry, 2011, 54, pp. 7280-7288 in toluene (1 mL), phenyl isocyanate (36 μL) and triethylamine (46 μL) were added at room temperature, and the mixture was stirred at 60° C. for 4 hours and 40 minutes. To the reaction mixture, phenyl isocyanate (36 μL) and triethylamine (46 μL) were added, and the mixture was further stirred at 60° C. for 6 hours. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were added to the reaction mixture. The organic layer was separated, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 5-(3-(2-((tert-butyldimethylsilyl)oxy)ethyl)isoxazol-5-yl)-N2-(3-fluorophenyl)-N4-propylpyrimidine-2,4-diamine (S4, 22 mg).

Workup

  1. stirringthe mixture was further stirred at 60° C. for 6 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-29b4cb1020b54c4d91d01c25ef447916
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

Loading…