1,2-Dimethoxyethane → HCID 118051738, compound

HRID 595865Notes

Reaction equation

HRID 595865 reaction equation
[CH3:1][S:2]([O:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH:8]([C:12]2[CH:17]=[N:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14](Br)[N:13]=2)[CH2:7]1)(=[O:4])=[O:3].[CH2:26]([NH:33][C:34]([C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][C:37]=1[F:45])=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.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]>[CH3:1][S:2]([O:5][C@H:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([C:12]2[CH:17]=[N:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([C:39]3[CH:40]=[CH:41][C:36]([C:34](=[O:35])[NH:33][CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[C:37]([F:45])[CH:38]=3)[N:13]=2)[CH2:7]1)(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 44717404[4-(Benzylcarbamoyl)-3-fluorophenyl]boronic acidHCID 131734601HCID 131734601, compound

Product 1

HCID 118051738HCID 118051738, compoundYield 101%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To cis racemate (+/−)-3-(6-bromo-5-pivalamidopyrazin-2-yl)cyclohexyl methanesulfonate (54 mg, 0.124 mmol) in 2.0 mL MW vial was added (4-(benzylcarbamoyl)-3-fluorophenyl)boronic acid (50.9 mg, 0.186 mmol), PdCl2(dppf) (9.10 mg, 0.012 mmol), DME (1166 μL) and 2M Na2CO3 solution (389 μL). The reaction mixture was heated at microwave synthesizer (12 min, 80° C.). The reaction mixture was diluted with EtOAc and washed with water three times, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography eluting with 0-100% of EtOAc (containing 10% of MeOH) to provide 73 mg of (+/−)-(1S,3R)-3-(6-(4-(benzylcarbamoyl)-3-fluorophenyl)-5-pivalamidopyrazin-2-yl)cyclohexyl methanesulfonate which was taken to the next reaction without further purification. LCMS (m/z): 583.4 (MH+), 0.87 min.

Workup

  1. washwashed with water three times
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography
  6. washeluting with 0-100% of EtOAc (containing 10% of MeOH)

Sources & evidence

ORD record
ord-7e4808ac23b248f3957a0f0ce2090e39
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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