Sodium Carbonate → HCID 118046170, compound

HRID 595935Notes

Reaction equation

HRID 595935 reaction equation
[CH2:1]([NH:8][C:9](=[O:25])[C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:27]1[C:28]([NH2:33])=[N:29][CH:30]=[CH:31][N:32]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:33][C:28]1[C:27]([C:13]2[CH:12]=[CH:11][C:10]([C:9]([NH:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:25])=[CH:15][CH:14]=2)=[N:32][CH:31]=[CH:30][N:29]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2762242-Amino-3-chloropyrazineHCID 46739041N-Benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 118046170HCID 118046170, compoundYield 59.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (150 mg, 0.445 mmol), 3-chloropyrazin-2-amine (74.9 mg, 0.578 mmol), and PdCl2(dppf)-CH2Cl2 adduct (36.3 mg, 0.044 mmol) in DME (3.3 mL) was added 2 M Na2CO3 (1.11 mL). The reaction mixture was heated at microwave synthesizer (120° C., 10 min). Diluted with EtOAc and washed with water twice. Then extracted with 1N HCl (3×15 mL). The acidic solution was washed with ether twice (2×15 mL), and then basified with Na2CO3. Followed by extracting with EtOAc (20 mL, 3 times) and then washed by sat NaHCO3, water and brine, dried over Na2SO4 and filtered off, concentrated. The crude product was purified with flash chromatography eluting with 0-100% of EtOAc(containing 10% MeOH) in heptane, then concentrated on rotavap. The residue was triturated with ether to provide 80.2 mg of desired product. LCMS (m/z): 305.2 (MH+), 0.59 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (d, J=8.22 Hz, 1H) 8.41 (s, 1H) 8.06 (dd, J=9.39, 2.74 Hz, 1H) 8.01 (d, J=8.61 Hz, 2H) 7.94 (br. s., 1H) 7.83 (d, J=8.22 Hz, 2H) 7.40-7.34 (m, 2H) 7.30 (t, J=7.63 Hz, 2H) 7.22 (d, J=7.43 Hz, 1H) 6.40 (d, J=9.39 Hz, 1H) 5.12-5.03 (m, 1H) 3.75-3.60 (m, 2H).

Workup

  1. washwashed with water twice
  2. extractionThen extracted with 1N HCl (3×15 mL)
  3. washThe acidic solution was washed with ether twice (2×15 mL)
  4. extractionFollowed by extracting with EtOAc (20 mL, 3 times)
  5. washwashed
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered off
  8. concentrationconcentrated
  9. customThe crude product was purified with flash chromatography
  10. washeluting with 0-100% of EtOAc(containing 10% MeOH) in heptane
  11. concentrationconcentrated on rotavap
  12. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-89fef6e16dc54aef8bd86fa2305460de
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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