Potassium Carbonate → 2-(4-(isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

HRID 271400Notes

Reaction equation

HRID 271400 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][N:11]3[C:14](=[O:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.ClC1C=CC(C2N=CN=C(NNC(OC(Cl)(Cl)Cl)=O)C=2C2C=CC=CC=2)=CC=1.Br[CH2:53][C:54]1[CH:59]=[CH:58][C:57]([C:60]2[O:64][N:63]=[CH:62][CH:61]=2)=[CH:56][CH:55]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[O:64]1[C:60]([C:57]2[CH:58]=[CH:59][C:54]([CH2:53][N:15]3[C:14](=[O:17])[N:11]4[CH:12]=[N:13][C:8]([C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=5)=[C:9]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[C:10]4=[N:16]3)=[CH:55][CH:56]=2)=[CH:61][CH:62]=[N:63]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 229975455-(4-(Bromomethyl)phenyl)isoxazoleHCID 58772821Trichloromethyl 2-(6-(4-chlorophenyl)-5-phenylpyrimidin-4-yl)hydrazinecarboxylateHCID 587728227-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

Product 1

HCID 159536642-(4-(isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 7-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one and/or trichloromethyl 2-(6-(4-chlorophenyl)-5-phenylpyrimidin-4-yl)hydrazinecarboxylate (16.0 mg, 0.05 mmol) in acetone (5 mL) at room temperature under argon was added 5-(4-(bromomethyl)phenyl)isoxazole (23.8 mg, 0.10 mmol), followed by K2CO3 (13.8 mg, 0.10 mmol). The resulting mixture was heated at 60° C. for 17 h. Insoluble material was filtered and rinsed with CH2Cl2. The filtrate was concentrated under reduced pressure and purified by reverse phase preparative HPLC (without TFA). Further purification was performed by silica gel column chromatography eluting with EtOAc-hexanes. Pure product was lyophilized from 1,4-dioxane to obtain the title compound (3.5 mg) as an off-white lyophilate. HPLC/MS: retention time=3.88 min, [M+H]30 =480. 1H NMR (CDCl3): δ 8.71 (s, 1H), 8.28 (d, J=1.2 Hz, 1H), 7.81 (d, J=7.3 Hz, 2H), 7.45 (d, J=7.3 Hz, 2H), 7.26-7.42 (m, 7H), 7.18 (d, J=7.2 Hz, 2H), 6.51(d, J=1.2 Hz, 1H), 5.18 (s, 2H).

Workup

  1. filtrationInsoluble material was filtered
  2. washrinsed with CH2Cl2
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified by reverse phase preparative HPLC (without TFA)
  5. customFurther purification
  6. washeluting with EtOAc-hexanes

Sources & evidence

ORD record
ord-6868ff5e5a794a9fbb0c02bb755a4d16
Source dataset
uspto-grants-2008_11
Patent number
US07452892B2

Reaction notes

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