Sodium Carbonate → [4-(6'-Isopropylamino-[2,2';4',3'']terpyridin-5''-yl)-phenyl]-(4-isopropyl-piperazin-1-yl)-methanone

HRID 1798490Notes

Reaction equation

HRID 1798490 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]([NH:46][CH:47]([CH3:49])[CH3:48])[N:43]=[C:42]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=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]>[CH:47]([NH:46][C:44]1[N:43]=[C:42]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=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)([CH3:49])[CH3:48]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 68733072(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-isopropyl-amineHCID 68756040(4-Isopropyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone2×

Product 1

HCID 68732771[4-(6'-Isopropylamino-[2,2';4',3'']terpyridin-5''-yl)-phenyl]-(4-isopropyl-piperazin-1-yl)-methanone

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) (1.2 eq, 0.162 mmol, 58 mg) and 2M Na2CO3 (2.0 eq, 0.262 mmol, 0.13 ml) in DME (1 ml) are added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-isopropyl-amine (Ex. 2.46; step1) (1 eq, 0.131 mmol, 50 mg) and [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.0131 mmol, 9.6 mg). The reaction mixture is heated using microwave radiation at 90° C. for 3 hours. 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 residue is purified by reverse phase 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 and 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 521.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 3 hours
  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 residue is purified by reverse phase 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 and 2M NH3 in MeOH
  13. concentrationconcentrated in vacuo
  14. customdried under vacuum

Sources & evidence

ORD record
ord-cec8869ad82f4a5f9c45adf4c1109d5a
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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