Tetrahydrofuran → 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

HRID 2092310Notes

Reaction equation

HRID 2092310 reaction equation
[CH3:1][C:2]1[C:11]([NH2:12])=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl[C:25]1[C:30]([C:31]2[N:36]=[CH:35][N:34]=[C:33]([NH:37][CH3:38])[CH:32]=2)=[CH:29][CH:28]=[CH:27][N:26]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>O.C(OCC)(=O)C.O1CCOCC1>[CH3:1][C:2]1[C:11]([NH:12][C:25]2[C:30]([C:31]3[CH:32]=[C:33]([NH:37][CH3:38])[N:34]=[CH:35][N:36]=3)=[CH:29][CH:28]=[CH:27][N:26]=2)=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 589422526-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amineHCID 673386327-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

Product 1

HCID 673392747-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 7-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine (0.083 g, 0.26 mmol) and 6-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amine (0.058 g, 0.26 mmol) were placed in a clear microwave vial along with 3 ml of dioxane. While stirring, lithium bis(trimethylsilyl)amide in THF (1.6 ml, 1.6 mmol) was added dropwise with a syringe to the reaction. The vial was capped and heated in a Personal Chemistry Smith Synthesizer to 150° C. for 12 minutes. The reaction was diluted with water and ethyl acetate. The organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The residue was purified by HPLC using a gradient of 5% ACN 0.1% TFA to 95% ACN 0.1% TFA in water 0.1% TFA. The pure fractions were neutralized with ammonium hydroxide and the volatiles were removed under reduced pressure. The solid that crashed out of the aqueous layer was filtered off, washed with with water and dried in a vacuum oven at 45 degrees to give 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine as a light yellow solid. MS (M+H)+ 474.

Workup

  1. customThe vial was capped
  2. washThe organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  3. customThe residue was purified by HPLC
  4. customthe volatiles were removed under reduced pressure
  5. filtrationwas filtered off
  6. washwashed with with water
  7. customdried in a vacuum oven at 45 degrees

Sources & evidence

ORD record
ord-48b6cd62d9414cff9af3e9419d9a98d9
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

Loading…