1,2-Dimethoxyethane → HCID 118046500, compound

HRID 595886Notes

Reaction equation

HRID 595886 reaction equation
Br[C:2]1[C:3]([NH2:14])=[N:4][CH:5]=[C:6]([CH2:8][CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])[N:7]=1.[CH2:15]([NH:22][C:23](=[O:40])[C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][C:25]=1[F:39])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>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.CO>[NH2:14][C:3]1[C:2]([C:27]2[CH:28]=[CH:29][C:24]([C:23]([NH:22][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:40])=[C:25]([F:39])[CH:26]=2)=[N:7][C:6]([CH2:8][CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 80711,2-Dimethoxyethane2×HCID 10340Sodium CarbonateHCID 118046216HCID 118046216, compoundHCID 131734602HCID 131734602, compound

Product 1

HCID 118046500HCID 118046500, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent

Procedure

To 3-bromo-5-(2-(methylsulfonyl)ethyl)pyrazin-2-amine (126 mg, 0.405 mmol) was added N-benzyl-2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (144 mg, 0.405 mmol), PdCl2(dppf)-CH2Cl2 adduct (33.1 mg, 0.040 mmol), DME (1.5 mL) and then sodium carbonate 2 M aqueous solution (0.607 mL, 1.214 mmol). The reaction was microwave at 125° C. for 12 min followed by LCMS. To the reaction was added 5 mL of DME and 5 mL of MeOH, filtered and concentrated to residue. The crude was dissolved in 2.5 mL of DMSO, filtered, purified by prep HPLC and lyophilized to TFA salt. To the TFA salt was added 200 mL of ethyl acetate, washed with saturated sodium carbonate (3×), water (3×), dried sodium sulfate, filtered and concentrated to constant mass to give 59 mg of the desired product 4-(3-amino-6-(2-(methylsulfonyl)ethyl)pyrazin-2-yl)-N-benzyl-2-fluorobenzamide as free base in 34% yield. LCMS (m/z): 429.2 (MH+), 0.65 min; 1H NMR (400 MHz, CD3OD) δ ppm 7.95 (s, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.67 (dd, J=8.0, 1.4 Hz, 1H), 7.59 (dd, J=11.7, 1.2 Hz, 1H), 7.29-7.42 (m, 4H), 7.20-7.28 (m, 1H), 4.59 (s, 2H), 3.48-3.57 (m, 2H), 3.18 (dd, J=9.0, 6.7 Hz, 2H), 2.96 (s, 3H).

Workup

  1. customat 125° C.
  2. customfor 12 min
  3. filtrationfiltered
  4. concentrationconcentrated to residue
  5. dissolutionThe crude was dissolved in 2.5 mL of DMSO
  6. filtrationfiltered
  7. custompurified by prep HPLC
  8. additionTo the TFA salt was added 200 mL of ethyl acetate
  9. washwashed with saturated sodium carbonate (3×), water (3×), dried sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to constant mass

Sources & evidence

ORD record
ord-3bac691769994573ae2f22b72bb57c64
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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