Potassium Carbonate → [2-(1H-Indol-4-yl)-ethyl]-(6-pyridin-3-yl-2-pyridin-2-yl-pyrimidin-4-yl)-amine

HRID 1668654Notes

Reaction equation

HRID 1668654 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:3]=1.[NH:20]1[C:28]2[C:23](=[C:24]([CH2:29][CH2:30][NH2:31])[CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[NH:20]1[C:28]2[C:23](=[C:24]([CH2:29][CH2:30][NH:31][C:2]3[CH:7]=[C:6]([C:8]4[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=4)[N:5]=[C:4]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=4)[N:3]=3)[CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 131009012-(1H-Indol-4-yl)ethan-1-amineHCID 283091114-Chloro-2-(pyridin-2-yl)-6-(pyridin-3-yl)pyrimidine2×

Product 1

HCID 24862800[2-(1H-Indol-4-yl)-ethyl]-(6-pyridin-3-yl-2-pyridin-2-yl-pyrimidin-4-yl)-amine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-Chloro-6-pyridin-3-yl-2-pyridin-2-yl-pyrimidine (Intermediate A) (1 eq, 50 mg) in NMP (1 ml) is treated with 2-(1H-indol-4-yl)-ethylamine (1.1 eq, 33 mg) followed by K2CO3 (5 eq, 178 mg). The reaction mixture is heated using microwave radiation at 120° C. for 45 minutes. After cooling to room temperature, the mixture is partitioned between EtOAc/water and the organic portion is separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA) and the appropriate fractions are combined and concentrated in vacuo. The resulting residue is loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and dried under vacuum to afford the title compound [M+H]+=393.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 120° C.
  3. customfor 45 minutes
  4. customthe mixture is partitioned between EtOAc/water
  5. customthe organic portion is separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. washeluting with MeOH
  12. concentrationThe methanolic ammonia fractions are concentrated in vacuo
  13. customdried under vacuum

Sources & evidence

ORD record
ord-533561f539324e3e8a4ab808c66e511c
Source dataset
uspto-grants-2011_08
Patent number
US07989458B2

Reaction notes

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