Sodium Carbonate → 4-[4-(6'-Methylamino-[2,2';4',3'']terpyridin-5''-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1798542Notes

Reaction equation

HRID 1798542 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17](B3OC(C)(C)C(C)(C)O3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].Br[C:35]1[CH:36]=[C:37]([C:41]2[CH:46]=[C:45]([NH:47][CH3:48])[N:44]=[C:43]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=3)[CH:42]=2)[CH:38]=[N:39][CH:40]=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]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:35]3[CH:36]=[C:37]([C:41]4[CH:46]=[C:45]([NH:47][CH3:48])[N:44]=[C:43]([C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=5)[CH:42]=4)[CH:38]=[N:39][CH:40]=3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 86633643(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

Product 1

HCID 687582624-[4-(6'-Methylamino-[2,2';4',3'']terpyridin-5''-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

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-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Intermediate B20) (1.5 eq, 1.095 mmol, 0.413 g) and 2M Na2CO3 (2.0 eq, 1.460 mmol, 0.730 ml) in DME (5 ml) is added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-methyl-amine (Example 2.1, step1) (1 eq, 0.730 mmol, 0.249 g) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.073 mmol, 0.059 g). 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 crude residue is purified by flash chromatography (0-100% EtOAc in iso-hexane and up to 10% MeOH in EtOAc), to afford title compound.

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 crude residue is purified by flash chromatography (0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-aa0bfdbd29c64685a87e39c67b5165c5
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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