2-(Tributylstannyl)-1,3-thiazole → N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(thiazol-2-yl)phthalazin-1-amine

HRID 593958Notes

Reaction equation

HRID 593958 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[C:25]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH3:33])[N:27]=4)=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:15][CH:14]=2)=[N:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:39]1[S:40][CH:41]=[CH:42][N:43]=1)CCC>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>[CH3:33][NH:32][C:28]1[N:27]=[C:26]([C:25]2[C:20]([O:19][C:16]3[CH:17]=[CH:18][C:13]([NH:12][C:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C:2]([C:39]5[S:40][CH:41]=[CH:42][N:43]=5)=[N:3][N:4]=4)=[CH:14][CH:15]=3)=[N:21][CH:22]=[CH:23][CH:24]=2)[CH:31]=[CH:30][N:29]=1

Participants

4

Reactant 2

HCID 27632592-(Tributylstannyl)-1,3-thiazoleHCID 426043304-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine

Product 1

HCID 42605079N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(thiazol-2-yl)phthalazin-1-amine

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

A resealable pressure tube, purged with argon, was charged with 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine (150 mg, 0.329 mmol), tetrakis(triphenylphosphine)palladium (38 mg, 0.033 mmol), and 2-(tributylstannyl)thiazole (0.207 mL, 0.658 mmol). This mixture was purged with argon for 10 minutes, followed by addition of toluene (1.6 ml, 0.2 M). Tube was sealed and mixture heated to 110° C. overnight. Next day LC/MS shows completion of reaction. The reaction was stopped, cooled to RT and concentrated under reduced pressure to a brown residue. This residue was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA). The product-containing fractions were combined, basified by addition of aq. NaHCO3 and extracted with ethyl acetate. The organic portion was dried with Na2SO4, filtered, and concentrated to afford pure N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(thiazol-2-yl)phthalazin-1-amine as a yellow solid. MS m/z=505 [M+H]+. Calc'd for C27H20N8OS: 504.57.

Workup

  1. customA resealable pressure tube, purged with argon
  2. customThis mixture was purged with argon for 10 minutes
  3. additionfollowed by addition of toluene (1.6 ml, 0.2 M)
  4. customTube was sealed
  5. customcompletion of reaction
  6. temperaturecooled to RT
  7. concentrationconcentrated under reduced pressure to a brown residue
  8. customThis residue was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA)
  9. additionbasified by addition of aq. NaHCO3
  10. extractionextracted with ethyl acetate
  11. dry with materialThe organic portion was dried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-899ad2af034d4594bef72152193c134a
Source dataset
uspto-grants-2016_01
Patent number
US09242961B2

Reaction notes

Loading…