Dimethylformamide → 9-Phenyl-2-(3-pyridyl)purine-6-carboxamide

HRID 391618Notes

Reaction equation

HRID 391618 reaction equation
[NH2:1][C:2]1[C:3]([C:21]([O:23]C)=O)=[N:4][C:5]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[N:6]C=1NC1C=CC=CC=1.NC1C(C(OC)=O)=NC(Cl)=NC=1N[C:33]1[CH:38]=[CH:37]C=[CH:35][CH:34]=1.C([Sn](CCCC)(CCCC)C1C=[N:51]C=CC=1)CCC.[CH3:63][N:64]([CH:66]=O)[CH3:65]>>[C:65]1([N:64]2[CH:66]=[N:1][C:2]3[C:63]2=[N:6][C:5]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[N:4][C:3]=3[C:21]([NH2:51])=[O:23])[CH:37]=[CH:38][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 34838483-(Tributylstannyl)pyridineHCID 57474558Methyl 5-amino-2-chloro-6-(phenylamino)pyrimidine-4-carboxylateHCID 57474559Methyl 5-amino-6-(phenylamino)-2-(3-pyridyl)pyrimidine-4-carboxylate

Product 1

HCID 249378619-Phenyl-2-(3-pyridyl)purine-6-carboxamideYield 57%

Conditions

Temperature
120 °C

Procedure

Methyl 5-amino-6-(phenylamino)-2-(3-pyridyl)pyrimidine-4-carboxylate. To a solution of methyl 5-amino-2-chloro-6-(phenylamino)pyrimidine-4-carboxylate (0.189 g, 0.68 mmol) in anhydrous DMF (3.5 mL) was added 3-(tributylstannyl)pyridine (1.252 g, 3.4 mmol), and dichlorobis(triphenylphosphine) palladium(II) (0.239 g, 0.34 mmol). The solution was purged with nitrogen then heated in an Emrys Optimizer microwave reactor for 30 minutes at 120° C. The volatiles were evaporated and the resulting residue was purified using chromatography on a normal phase silica gel column (1-10% methanol in dichloromethane). Fractions containing product were combined and the solvent evaporated. The material was re-purified using reverse-phase preparatory HPLC (30-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 minutes). Fractions containing the desired material were combined and concentrated under reduced pressure before being passed through a Strata-XC ion exchange column with water, methanol, and 5% ammonium hydroxide in methanol. The resulting solid was dried under high vacuum at 60° C. to afford the title compound (0.125 g, 0.389 mmol, 57% yield). MS (ESI) m/z 322.4 [M+1]+.

Workup

  1. customThe solution was purged with nitrogen
  2. customThe volatiles were evaporated
  3. customthe resulting residue was purified
  4. additionFractions containing product
  5. customthe solvent evaporated
  6. customThe material was re-purified
  7. customreverse-phase preparatory HPLC (30-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 minutes)
  8. additionFractions containing the desired material
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting solid was dried under high vacuum at 60° C.

Sources & evidence

ORD record
ord-612f1fbbb7a94a009b1581459b05b187
Source dataset
uspto-grants-2013_02
Patent number
US08383634B2

Reaction notes

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