Sodium Carbonate → tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-(1H-indazol-4-yl)oxazol-5-yl)phenyl)piperazine-1-carboxylate

HRID 714970Notes

Reaction equation

HRID 714970 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](I)[O:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2].CC1(C)C(C)(C)OB([C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[N:42][NH:43]3)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[N:42][NH:43]3)[O:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 454801864-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 68522092Tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-iodooxazol-5-yl)phenyl)piperazine-1-carboxylate

Product 1

HCID 59587447tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-(1H-indazol-4-yl)oxazol-5-yl)phenyl)piperazine-1-carboxylateYield 47%

Reagents, catalysts & solvents 5

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-iodooxazol-5-yl)phenyl)piperazine-1-carboxylate (0.080 g, 0.15 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-1H-indazole (0.080 g, 0.33 mmol) and sodium carbonate (0.048 g, 0.45 mmol) in toluene (0.81 ml), ethanol (0.49 ml) and water (0.23 ml) was added bis(triphenylphosphine)palladium (II) chloride (0.005 g, 0.007 mmol) and the resulting mixture heated in the microwave at 120° C. for 60 minutes followed by an additional 45 minutes. The reaction mixture was diluted with EtOAc and washed with 1M NaOH. The organic phase was passed through a MP-SH cartridge, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by silica gel column chromatography using a 10-100% EtOAc in hexane gradient to afford tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-(1H-indazol-4-yl)oxazol-5-yl)phenyl)piperazine-1-carboxylate (0.037 g, 0.07 mmol, 47%) as a yellow solid. LCMS (2) Rt: 3.57 min; m/z (ES+) 518.

Workup

  1. washwashed with 1M NaOH
  2. dry with materialdried over MgSO4
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7531e91d42994fc292d597473a56c337
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

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