1,2-Dimethoxyethane → HCID 131734597, compound

HRID 595858Notes

Reaction equation

HRID 595858 reaction equation
Br[C:2]1[C:3]([NH2:22])=[N:4][CH:5]=[C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:9]2)[N:7]=1.[CH2:23]([NH:30][C:31]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][C:34]=1[F:42])=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=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].C(Cl)Cl>[NH2:22][C:3]1[C:2]([C:36]2[CH:37]=[CH:38][C:33]([C:31]([NH:30][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:32])=[C:34]([F:42])[CH:35]=2)=[N:7][C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:9]2)=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 44717404[4-(Benzylcarbamoyl)-3-fluorophenyl]boronic acidHCID 123354204HCID 123354204, compound

Product 1

HCID 131734597HCID 131734597, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To 3-bromo-5-(3-((tert-butyldimethylsilyl)oxy)cyclohexyl)pyrazin-2-amine (68 mg, 0.176 mmol) in 2 mL MW vial was added (4-(benzylcarbamoyl)-3-fluorophenyl)boronic acid (72.1 mg, 0.264 mmol), PdCl2(dppf)-DCM (12.88 mg, 0.018 mmol), DME (1.32 mL) and 2M Na2CO3 solution (0.44 mL). The reaction mixture was heated at microwave synthesizer (12 min, 120° 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)/heptane to provide 60 mg of crude cis racemate compound which was taken to the next reaction without further purification. LCMS (m/z): 535.4 (MH+), 1.31 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)/heptane
  7. customto provide 60 mg of crude cis racemate compound which
  8. customwas taken to the next reaction without further purification
  9. custom535.4 (MH+), 1.31 min.

Sources & evidence

ORD record
ord-f68506cfa7f44816af7ab55ba07e8f73
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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