Cesium carbonate → Methyl 2-(pyridin-3-ylamino)pyrimidine-5-carboxylate

HRID 1662857Notes

Reaction equation

HRID 1662857 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=1.Br[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>CCOC(C)=O.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].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>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([NH:1][C:2]2[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:7]=2)[CH:14]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 122863-BromopyridineHCID 312751,4-DioxaneHCID 9793866Methyl 2-aminopyrimidine-5-carboxylate

Product 1

HCID 59652725Methyl 2-(pyridin-3-ylamino)pyrimidine-5-carboxylateYield 141.9%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Two 20 mL microwave vials were each charged with methyl 2-aminopyrimidine-5-carboxylate (460.0 mg, 3.0 mmol), 3-bromopyridine (711.0 mg, 4.5 mmol), Pd2(dba)3 (110.0 mg, 0.12 mmol), XantPhos (208.3 mg, 0.36 mmol), Cs2CO3 (1.95 g, 6.0 mmol) and anhydrous dioxane (20 mL). The mixture was purged with argon gas for 15 min, then sealed and irradiated in a microwave (Initiator, Biotage) at 180° C. for 60 min. After cooling to room temperature, the cap was removed and the reaction mixtures were combined and diluted with ca. 100 mL of EtOAc. The resulting solution was concentrated in vacuo with ca. 15 g of silica gel. The loaded silica gel was taken to the ISCO system for further purification (80 g column, solid method, 0% to 20% MeOH gradient in DCM, 40 min method). Fractions, containing the product, were combined and concentrated in vacuo to give a reddish solid. The solid was washed with EtOAc (1×10 mL), Et2O (3×40 mL) and dried in vacuo to give the title compound as a fine beige powder (0.98 g, 47% yield).

Workup

  1. customThe mixture was purged with argon gas for 15 min
  2. customsealed
  3. customirradiated in a microwave (Initiator, Biotage) at 180° C. for 60 min
  4. customthe cap was removed
  5. customthe reaction mixtures
  6. concentrationThe resulting solution was concentrated in vacuo with ca. 15 g of silica gel
  7. customThe loaded silica gel was taken to the ISCO system for further purification (80 g column, solid method, 0% to 20% MeOH gradient in DCM, 40 min method)
  8. additionFractions, containing the product
  9. concentrationconcentrated in vacuo
  10. customto give a reddish solid
  11. washThe solid was washed with EtOAc (1×10 mL), Et2O (3×40 mL)
  12. customdried in vacuo

Sources & evidence

ORD record
ord-6ac97ae808ec4c948357a2a14f7eb715
Source dataset
uspto-grants-2011_10
Patent number
US08030487B2

Reaction notes

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