Sodium Carbonate → HCID 178424464, compound

HRID 1798507Notes

Reaction equation

HRID 1798507 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].Br[C:34]1[CH:35]=[C:36]([C:40]2[CH:45]=[C:44]([OH:46])[N:43]=[C:42]([C:47]3[CH:52]=[CH:51][CH:50]=[C:49]([CH3:53])[N:48]=3)[CH:41]=2)[CH:37]=[N:38][CH:39]=1>COCCOC.C(Cl)Cl.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]>[OH:46][C:44]1[N:43]=[C:42]([C:47]2[CH:52]=[CH:51][CH:50]=[C:49]([CH3:53])[N:48]=2)[CH:41]=[C:40]([C:36]2[CH:37]=[N:38][CH:39]=[C:34]([C:15]3[CH:14]=[CH:13][C:12]([C:10]([N:7]4[CH2:6][CH2:5][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:9][CH2:8]4)=[O:11])=[CH:17][CH:16]=3)[CH:35]=2)[CH:45]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 68756040(4-Isopropyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone2×HCID 178424462HCID 178424462, compound

Product 1

HCID 178424464HCID 178424464, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of (4-Isopropyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone (Intermediate B4) (1.1 eq, 0.161 mmol, 57 mg) and 2M Na2CO3 (2.0 eq, 0.292 mmol, 0.15 ml) in DME (1 ml) is added 5″-Bromo-6-methyl-[2,2′;4′,3″]terpyridin-6′-ol (Example 2.109; step1) (1 eq, 0.146 mmol, 50 mg) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.015 mmol, 12 mg). The reaction mixture is heated using microwave radiation at 90° C. for 90 mins. The reaction mixture is dissolved in DCM and washed with water. The organic layer is washed with brine, dried over drying agent MgSO4, filtered and the organic solvent is reduced in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-20% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 494

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 90 mins
  4. washwashed with water
  5. washThe organic layer is washed with brine
  6. customdried
  7. dry with materialover drying agent MgSO4
  8. filtrationfiltered
  9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-20% acetonitrile in water—0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. dissolutionThe resulting residue is dissolved in MeOH
  12. washeluting with MeOH
  13. concentrationconcentrated in vacuo
  14. customdried under vacuum

Sources & evidence

ORD record
ord-a3ce2060375640d0b18730e164e1ec1a
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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