Potassium Iodide → HCID 67298108, compound

HRID 1520390Notes

Reaction equation

HRID 1520390 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[C:16]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:15]=[C:14]3[NH:27][CH3:28])[CH:8]=[CH:9][CH:10]=1.[F:29][C:30]([F:34])([F:33])[CH2:31][NH2:32].[I-].[K+].CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:28][NH:27][C:14]1[C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH2:3][CH2:2][NH:32][CH2:31][C:30]([F:34])([F:33])[F:29])[CH:6]=3)[CH:12]=2)[N:17]=[C:16]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:15]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 81531DiisopropylethylamineHCID 67298207HCID 67298207, compound

Product 1

HCID 67298108HCID 67298108, compoundYield 51.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a 10 mL microwave vial was added 6-(3-(2-chloroethoxy)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (50.0 mg, 0.128 mmol), 2,2,2-trifluoroethylamine (0.100 ml, 1.279 mmol), potassium iodide (42.5 mg, 0.256 mmol), and N,N′-diisopropylethylamine (0.045 ml, 0.256 mmol) in DMF (3 mL) to give a yellow suspension. The vial was irradiated at 150° C. in the microwave for 20 min. Water (10 mL) was added to the mixture and extracted with ethyl acetate (2×20 mL). The organic layers were combined and washed with water (1×20 mL) and brine (1×20 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with (CH2Cl2/CH2Cl2-MeOH-NH4OH=100:20:1 1:0 to 0:1). The product was converted to the HCl salt by addition of 4 M HCl-dioxane, then crystallization from IPA-H2O to give 30 mg of N-methyl-2-(pyridin-3-yl)-6-(3-(2-(2,2,2-trifluoroethylamino)ethoxy)phenyl)quinazolin-4-amine as a yellow powder (42%). LCMS m/z=454 (M+1) (Method C) (retention time=2.26 min). 1H NMR (300 MHz, DMSO) δ 10.73-10.36 (m, 1H), 9.65 (s, 1H), 9.13-8.98 (m, 2H), 8.93 (d, J=5.0 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H), 8.24 (d, J=7.7 Hz, 1H), 7.94-7.75 (m, 1H), 7.69-7.41 (m, 3H), 7.09 (d, J=8.1 Hz, 1H), 4.61-4.43 (m, 2H), 4.28-4.07 (m, 2H), 3.59-3.39 (m, 2H), 3.30 (d, J=2.8 Hz, 3H).

Workup

  1. customto give a yellow suspension
  2. customThe vial was irradiated at 150° C. in the microwave for 20 min
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washwashed with water (1×20 mL) and brine (1×20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (
  9. washeluted with (CH2Cl2/CH2Cl2-MeOH-NH4OH=100:20:1 1:0 to 0:1)
  10. additionThe product was converted to the HCl salt by addition of 4 M HCl-dioxane
  11. customcrystallization from IPA-H2O

Sources & evidence

ORD record
ord-9177a87e164947009ef9a4016c22c1ab
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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