Sodium Carbonate → HCID 44197933, compound

HRID 1970955Notes

Reaction equation

HRID 1970955 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[N:11]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=2)[CH2:27][CH2:26]1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([C:12]1[CH:13]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:35]3[CH:34]=[CH:33][C:32]([CH2:31][N:28]4[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]4)=[CH:37][CH:36]=3)[CH:3]=2)[N:9]=[C:10]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[N:11]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 454965984-((4-Methylpiperazin-1-yl)methyl)phenylboronic acidHCID 68773882HCID 68773882, compound

Product 1

HCID 44197933HCID 44197933, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 20074477Dimethoxyethane ethanolSolvent

Procedure

To a solution of 4-(5-bromo-pyridin-3-yl)-6-tert-butyl-2-pyridin-2-yl-pyrimidine (1 eq, 200 mg, 0.542 mmol) in EtOH/DME (2 ml, 1:1) is added 4-(4-methyl-piperazin-1-ylmethyl)-phenyl-boronic acid (1.1 eq, 174 mg, 0.596 mmol), aqueous Na2CO3 solution (2 M, 3 eq, 0.812 ml, 1.63 mmol) and Pd(PPh3)4 (0.05 eq, 31 mg, 0.027 mmol). The resulting mixture is heated using microwave radiation for 20 min at 140° C. The mixture is filtered, washed with DCM and concentrated in vacuo. The residue is partitioned between sat. aqueous NaHCO3 solution and DCM and the organic layer is washed with brine, dried (MgSO4) concentrated under reduced pressure. The resulting residue is purified by reverse phase chromatography yielding the title compound; [M+H]+=479. 1H NMR (CDCl3, 400 MHz): 9.26 (d, 1H), 8.95 (d, 1H), 8.87 (m, 1H), 8.66 (t, 1H), 8.62 (m, 1H), 7.88 (td, 1H), 7.77 (s, 1H), 7.64 (d, 2H), 7.47 (d, 2H), 7.41 (ddd, 1H), 3.58 (s, 2H), 2.60-2.43 (m, 8H), 2.32 (s, 3H), 1.51 (s, 9H).

Workup

  1. temperatureThe resulting mixture is heated
  2. customfor 20 min
  3. customat 140° C
  4. filtrationThe mixture is filtered
  5. washwashed with DCM
  6. concentrationconcentrated in vacuo
  7. customThe residue is partitioned between sat. aqueous NaHCO3 solution and DCM
  8. washthe organic layer is washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue is purified by reverse phase chromatography

Sources & evidence

ORD record
ord-c23913768ebf4755887712dd705babaa
Source dataset
uspto-grants-2013_04
Patent number
US08431578B2

Reaction notes

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