Sodium Carbonate → HCID 24863588, compound

HRID 2092301Notes

Reaction equation

HRID 2092301 reaction equation
I[C:2]1[C:3]([CH3:25])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[N:8]=[C:7]2[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=1.[CH3:26][NH:27][C:28]1[N:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=2)[N:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:12][C:9]1[N:8]=[C:7]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=2)[C:6]2[C:11](=[C:2]([C:33]3[CH:34]=[C:35]4[C:30](=[CH:31][CH:32]=3)[N:29]=[C:28]([NH:27][CH3:26])[N:37]=[CH:36]4)[C:3]([CH3:25])=[CH:4][CH:5]=2)[N:10]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16086139N-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)quinazolin-2-amineHCID 67338962HCID 67338962, compound

Product 1

HCID 24863588HCID 24863588, compoundYield 79.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

8-Iodo-2,7-dimethyl-N-(3-(trifluoromethoxy)phenyl)quinazolin-4-amine (0.250 g, 0.544 mmol), N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-2-amine (0.186 g, 0.653 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0629 g, 0.0544 mmol) and 2 M aqueous sodium carbonate (0.544 mL, 1.09 mmol) were placed in a microwave vial and dioxane (3 mL) was added. The tube was capped and heated in a microwave reactor at 150° C. for 10 min. The mixture was concentrated in vacuo and the residue dissolved in ethyl acetate and washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was dried with sodium sulfate and then purified by column chromatography on silica gel using a gradient of 20 to 80% EtOAc in hexanes. The clean fractions were combined and concentrated under vacuum to give a yellow film. The film was triturated with a 1:1 mixture of ether and hexanes. This resulted in the formation of an off-white solid which was collected by filtration and dried in a vacuum oven to give 6-(2,7-dimethyl-4-(3-(trifluoro-methoxy)phenylamino)quinazolin-8-yl)-N-methylquinazolin-2-amine (0.212 g, 79%). MS (M+H)+ 491.

Workup

  1. additionwas added
  2. customThe tube was capped
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate
  5. washwashed (2×) with an aqueous saturated solution of sodium bicarbonate
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. custompurified by column chromatography on silica gel using a gradient of 20 to 80% EtOAc in hexanes
  8. concentrationconcentrated under vacuum
  9. customto give a yellow film
  10. customThe film was triturated with a 1:1 mixture of ether and hexanes
  11. customThis resulted in the formation of an off-white solid which
  12. filtrationwas collected by filtration
  13. customdried in a vacuum oven

Sources & evidence

ORD record
ord-e2af14561386492d965c2fe569cbd636
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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