Cesium carbonate → N-(5-(4-methylpiperazin-1-yl)piridin-2-yl)-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidin-2-amine

HRID 526060Notes

Reaction equation

HRID 526060 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[CH:30][C:31]([NH2:34])=[N:32][CH:33]=2)[CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[CH:30][C:31]([NH:34][C:2]3[N:3]=[C:4]([O:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=4)[C:5]4[S:10][CH:9]=[CH:8][C:6]=4[N:7]=3)=[N:32][CH:33]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 223298335-(4-Methylpiperazin-1-yl)pyridin-2-amineHCID 866828282-Chloro-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidine

Product 1

HCID 89542484N-(5-(4-methylpiperazin-1-yl)piridin-2-yl)-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidin-2-amineYield 70.1%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

0.6 g (1.94 mmol) of the compound obtained in Step 3 of Example 1 and 0.75 g (3.88 mmol) of 5-(4-methylpiperazin-1-yl)piridin-2-amine were dissolved in 8 ml of 1,4-dioxane, and 178 mg (0.2 mmol) of tris(dibenzylideneacetone)dipalladium(O) and 122 mg (0.2 mmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthy were added thereto, and stirred for 5 minutes at room temperature. 1.27 g (3.88 mmol) of cesium carbonate was added thereto, and stirred for 3 hours at 100° C. Upon the completion of the reaction, the resulting mixture was cooled to room temperature and filtered over a short bed of Celite filter, and diluted with dichloromethane and washed with water. The organic layer was separated, dried over anhydrous Na2SO4, and filtered and distilled under a reduced pressure. The resulting residue was separated by column chromatography (dichloromethane:methanol (20:1, v/v)) to obtain 630 mg of the title compound (yield: 70%).

Workup

  1. stirringstirred for 3 hours at 100° C
  2. customUpon the completion of the reaction
  3. temperaturethe resulting mixture was cooled to room temperature
  4. filtrationfiltered over a short bed of Celite
  5. filtrationfilter
  6. additiondiluted with dichloromethane
  7. washwashed with water
  8. customThe organic layer was separated
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. distillationdistilled under a reduced pressure
  12. customThe resulting residue was separated by column chromatography (dichloromethane:methanol (20:1

Sources & evidence

ORD record
ord-196147ac85064edeac4603c4af03468d
Source dataset
uspto-grants-2016_05
Patent number
US09345719B2

Reaction notes

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