Pyridine → HCID 51030082, compound

HRID 2036817Notes

Reaction equation

HRID 2036817 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[N:10][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([CH:26]=2)[C:22]([NH:24][NH2:25])=[O:23])=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:36](=O)[C:37]([O:39][CH3:40])=[O:38].C(=O)([O-])[O-].[K+].[K+].S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.N1C=CC=CC=1>C(Cl)Cl.O>[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[N:10][C:11]([C:17]2[CH:26]=[C:21]([C:22]4[O:23][C:36]([C:37]([O:39][CH3:40])=[O:38])=[N:25][N:24]=4)[CH:20]=[N:19][CH:18]=2)=[N:12]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 11430Potassium CarbonateHCID 67749Trifluoromethanesulfonic anhydrideHCID 79846Methyl chloroglyoxylateHCID 670559233-Pyridinecarboxylic acid, 5-[5-phenyl-4-[(2-pyridinylmethyl)amino]-2-quinazolinyl]-, hydrazide

Product 1

HCID 51030082HCID 51030082, compoundYield 79.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinohydrazide (from Example 185, 0.30 g, 0.66 mmol) in DCM at 0° C. was added methyl 2-chloro-2-oxoacetate (0.062 mL, 0.66 mmol) and potassium carbonate (0.273 g, 1.90 mmol). Upon completion of addition, the mixture was stirred at RT for 16 h. After this time, water was added and the mixture was extracted into DCM, dried and concentrated. The resulting residue was dissolved in DCM. Triflic anhydride (0.187 mL, 1.1 mmol) and pyridine (0.149 mL, 1.8 mmol) were added and the resulting mixture was stirred at RT for 16 h. At the conclusion of this period, the reaction mixture was quenched with water and extracted with DCM (100 mL). The DCM layer was washed with water and brine. Chromatographic purification provided methyl 5-(5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridin-3-yl)-1,3,4-oxadiazole-2-carboxylate (270 mg, 78% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.81 (s, 1H), 9.17 (s, 1H), 9.09 (s, 1H), 8.24 (d, J=4.4 Hz, 1H), 7.94 (d, J=7.2 Hz, 1H), 7.86 (t, J=7.6 Hz, 1H), 7.75-7.72 (t, J=7.6 Hz, 3H), 7.59-7.51 (m, 5H), 7.34 (d, J=7.2 Hz, 2H), 7.24 (t, J=6.4 Hz, 1H), 6.98 (t, J=3.2 Hz, 1H), 4.77 (d, J=4.0 Hz, 2H). LCMS Method Q: retention time 1.39 min; [M+1]=514.5; HPLC Method B: purity 98.1%, retention time=8.74 min.

Workup

  1. additionUpon completion of addition
  2. extractionthe mixture was extracted into DCM
  3. customdried
  4. concentrationconcentrated
  5. dissolutionThe resulting residue was dissolved in DCM
  6. stirringthe resulting mixture was stirred at RT for 16 h
  7. customAt the conclusion of this period, the reaction mixture was quenched with water
  8. extractionextracted with DCM (100 mL)
  9. washThe DCM layer was washed with water and brine
  10. customChromatographic purification

Sources & evidence

ORD record
ord-c37eaa1f9547493498a77055674cc1a5
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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