Ethyl Acetate → 2-[(S)-4-Boc-3-benzylpiperazinyl]-6-[3-methyl-1-(trimethylsilyl)ethoxymethyl-1H-indazol-5-yl]pyrazine

HRID 643352Notes

Reaction equation

HRID 643352 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16](Cl)[N:15]=2)[CH2:10][C@@H:9]1[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:36]=2)[N:31]([CH2:47][O:48][CH:49]([Si:51]([CH3:54])([CH3:53])[CH3:52])[CH3:50])[N:30]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.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]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16]([C:35]3[CH:36]=[C:37]4[C:32](=[CH:33][CH:34]=3)[N:31]([CH2:47][O:48][CH:49]([Si:51]([CH3:52])([CH3:54])[CH3:53])[CH3:50])[N:30]=[C:29]4[CH3:28])[N:15]=2)[CH2:10][C@@H:9]1[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 592622572-[(S)-4-Boc-3-benzylpiperazinyl]-6-chloropyrazineHCID 131728062[3-methyl-1-(trimethylsilyl)ethoxymethy-1H-indazol-5-yl]boronic acid pinacol ester

Product 1

HCID 686890392-[(S)-4-Boc-3-benzylpiperazinyl]-6-[3-methyl-1-(trimethylsilyl)ethoxymethyl-1H-indazol-5-yl]pyrazineYield 72.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

To a solution of 2-[(S)-4-Boc-3-benzylpiperazinyl]-6-chloropyrazine 115 (0.10 g, 0.258 mmol) and [3-methyl-1-(trimethylsilyl)ethoxymethy-1H-indazol-5-yl]boronic acid pinacol ester 117 (0.10 g, 0.258 mmol) in 1,2-dimethoxyethane (5 mL) was added saturated sodium carbonate solution (0.5 mL) and Pd(dppf)Cl2 (0.019 g, 0.026 mmol). The reaction mixture was heated in a microwave reactor at 140° C. for 15 minutes. Ethyl acetate (100 mL) was added. The organic layer was washed with water and brine. The organic layer was dried over sodium sulfate. The organic solvent was evaporated under reduced pressure. The crude product was purified by RP-HPLC to yield the desired 2-[(S)-4-Boc-3-benzylpiperazinyl]-6-[3-methyl-1-(trimethylsilyl)ethoxymethyl-1 H-indazol-5-yl]pyrazine 118 (0.115 g, 0.187 mmol).

Workup

  1. washThe organic layer was washed with water and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customThe organic solvent was evaporated under reduced pressure
  4. customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-3fde4b3002aa42a2a9b99ab75bc01ee1
Source dataset
uspto-grants-2010_04
Patent number
US07700601B2

Reaction notes

Loading…