Cesium carbonate → N-[4-(3-Pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-pyrimidine-2,5-diamine

HRID 1662801Notes

Reaction equation

HRID 1662801 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][N:3]=1.Br[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH2:21][CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)(=[O:20])=[O:19])=[CH:14][CH:13]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:24]1([CH2:23][CH2:22][CH2:21][S:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:1][C:2]3[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][N:3]=3)=[CH:13][CH:14]=2)(=[O:19])=[O:20])[CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 764905-Nitropyrimidin-2-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 529828661-(3-(4-Bromophenylsulfonyl)propyl)pyrrolidine

Product 1

HCID 58748692N-[4-(3-Pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-pyrimidine-2,5-diamine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-amino-5-nitropyrimidine (840 mg, 6.0 mmol) in 50 mL anhydrous 1,4-dioxane were added 1-[3-(4-bromo-benzenesulfonyl)-propyl]-pyrrolidine (2.9 g, 8.7 mmol), Xantphos, (690 mg, 1.2 mmol), Pd2(dba)3 (559 mg, 0.61 mmol) and Cs2CO3 (5.8 g, 18 mmol). The reaction mixture was stirred at 100° C. for 5 h under argon. The solvent was removed under reduced pressure. The resulting solution was extracted with CHCl3 (3×50 mL) and sat. NaHCO3 (50 mL). The organic layer was separated, washed with brine, dried over Na2SO4 and filtered. The organic solvent was removed and the crude product was purified by silica gel column with 20% CH3OH/CHCl3 as an eluent. The precipitated yellow solid was isolated by washed with acetone and dried in vacuo (1.2 g, 52%). The above product was hydrogenated in 100 mL methanol/ethyl acetate (v/v: 1:1) using Pd/C (10%, 1 g) for 2 h. The palladium catalyst was removed by filtration, and the solvent was evaporated. The pale yellow solid was isolated by washed with acetone/methanol (v/v 5:1) and dried in vacuo (550 mg, 49%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. extractionThe resulting solution was extracted with CHCl3 (3×50 mL) and sat. NaHCO3 (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customThe organic solvent was removed
  8. customthe crude product was purified by silica gel column with 20% CH3OH/CHCl3 as an eluent
  9. customThe precipitated yellow solid was isolated
  10. washby washed with acetone
  11. customdried in vacuo (1.2 g, 52%)
  12. customfor 2 h
  13. customThe palladium catalyst was removed by filtration
  14. customthe solvent was evaporated
  15. customThe pale yellow solid was isolated
  16. washby washed with acetone/methanol (v/v 5:1)
  17. customdried in vacuo (550 mg, 49%)

Sources & evidence

ORD record
ord-5d244feed07b417685a58c748d75e7d6
Source dataset
uspto-grants-2011_10
Patent number
US08030487B2

Reaction notes

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