Cesium carbonate → N-(2,6-dichloropyridin-4-yl)pyrimidin-5-amine

HRID 1045819Notes

Reaction equation

HRID 1045819 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([Cl:9])[CH:3]=1.Br[C:11]1[CH:12]=[N:13][CH:14]=[N:15][CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:9][C:4]1[CH:3]=[C:2]([NH:1][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[CH:7]=[C:6]([Cl:8])[N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 1376524-Amino-2,6-dichloropyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 58349121N-(2,6-dichloropyridin-4-yl)pyrimidin-5-amineYield 62%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

4-Amino-2,6-dichloropyridine (1.23 g, 7.55 mmol, 1.20 eq), 5-bromopyrimidine (1.0 g, 6.3 mmol, 1.0 eq), Cs2CO3 (2.87 g, 8.81 mmol, 1.40 eq), Pd2(dba)3 (289 mg, 0.503 mmol, 0.0800 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (437 mg, 0.755 mmol, 0.120 eq) and dioxane (16 mL) were added to a microwave vial. The vial was purged with argon, capped and heated at 100° C. for 18 h. After cooling the reaction was filtered over a plug of celite and the plug was washed with 5% MeOH/CH2Cl2. The solvents were removed in vacuo and the crude mixture was purified by flash chromatography on silica gel afforded 938 mg (62%) of the title compound as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 8.95 (s, 1H), 8.76 (s, 2H), 6.95 (s, 2H); [M+1]+: 241.1.

Workup

  1. customThe vial was purged with argon
  2. customcapped
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered over a plug of celite
  5. washthe plug was washed with 5% MeOH/CH2Cl2
  6. customThe solvents were removed in vacuo
  7. customthe crude mixture was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-53cef2108271416b810583aa205e8aa6
Source dataset
uspto-grants-2013_10
Patent number
US08569308B2

Reaction notes

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