Nitrogen → HCID 44197793, compound

HRID 1970947Notes

Reaction equation

HRID 1970947 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].N#N.Br[C:30]1[CH:31]=[C:32]([C:36]2[CH:41]=[CH:40][N:39]=[C:38]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=3)[N:37]=2)[CH:33]=[N:34][CH:35]=1.C(Cl)Cl>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:30]3[CH:35]=[N:34][CH:33]=[C:32]([C:36]4[CH:41]=[CH:40][N:39]=[C:38]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=5)[N:37]=4)[CH:31]=3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 947NitrogenHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 68731520HCID 68731520, compoundHCID 68733668HCID 68733668, compound

Product 1

HCID 44197793HCID 44197793, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A stirred solution of 4-(4-isopropylpiperazine-1-carbonyl)phenylboronic acid (Int. E) (1.2 eq, 53 mg) and 2M sodium carbonate solution (2 eq, 2 ml) in DME (1 ml) under an inert atmosphere of N2 is treated with 4-(5-bromo-pyridin-3-yl)-2-pyridin-2-yl-pyrimidine (Int. H) (1 eq, 50 mg) followed by PdCl2(dppf).DCM (0.1 eq, 13 mg). The mixture is heated using microwave radiation at 90° C. for 90 minutes and then allowed to cool to RT. The mixture is extracted with DCM and the organic extracts are washed with water. The solvent is removed in vacuo and the crude product is purified by reverse phase column chromatography (Isolute™ C18, 0-80% acetonitrile in water—0.1% TFA) and the appropriate fractions are combined and concentrated in vacuo. The 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 overnight to afford the title compound [M+H]+=465 as a yellow solid.

Workup

  1. temperatureThe mixture is heated
  2. customat 90° C.
  3. customfor 90 minutes
  4. extractionThe mixture is extracted with DCM
  5. washthe organic extracts are washed with water
  6. customThe solvent is removed in vacuo
  7. customthe crude product is purified by reverse phase column chromatography (Isolute™ C18, 0-80% acetonitrile in water—0.1% TFA)
  8. concentrationconcentrated in vacuo
  9. washeluting with MeOH
  10. concentrationThe methanolic ammonia fractions are concentrated in vacuo
  11. customdried under vacuum overnight

Sources & evidence

ORD record
ord-619b70f79b034be0a931ca488c872c6b
Source dataset
uspto-grants-2013_04
Patent number
US08431578B2

Reaction notes

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