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

HRID 1668653

Reaction equation

HRID 1668653 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][NH2:30])[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][NH:30][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 280302(1H-indol-4-yl)methanamineHCID 283091114-Chloro-2-(pyridin-2-yl)-6-(pyridin-3-yl)pyrimidine2×

Product 1

HCID 23653548(1H-Indol-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-yl-pyrimidin-4-yl)-amine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-chloro-6-pyridin-3-yl-2-pyridin-2-yl-pyrimidine (Intermediate A) (1 eq, 0.2 g), C-(1H-indol-4-yl)-methylamine (1.1 eq, 0.12 g) and K2CO3 (3 eq, 0.308 g) in NMP (6 ml) is heated using microwave radiation at 120° C. for 1 hour. 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 mass directed preparative HPLC eluting with 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]+=379.

Workup

  1. customat 120° C.
  2. customfor 1 hour
  3. customthe mixture is partitioned between EtOAc/water
  4. customthe organic portion is separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude residue is purified by mass
  9. washeluting with 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-b28b5156c4cc45c390324699be3e2f60
Source dataset
uspto-grants-2011_08
Patent number
US07989458B2

Linked notes

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