Dichloromethane → HCID 90310790, compound

HRID 1519147Notes

Reaction equation

HRID 1519147 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5](Br)=[CH:4][N:3]=1.[CH:9]1([C:13]2[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[C:14]=2[O:23][CH3:24])[CH2:12][CH2:11][CH2:10]1.C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>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]>[CH:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:5]3[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=3)=[C:15]([F:22])[C:14]=2[O:23][CH3:24])[CH2:10][CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 90310803HCID 90310803, compound

Product 1

HCID 90310790HCID 90310790, compoundYield 97%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

To a 1000 mL round-bottom flask were added a stir bar, 2-amino-5-bromopyrazine (19.95 g, 115.3 mmol), (4-cyclobutyl-2-fluoro-3-methoxyphenyl)boronic acid (25.0 g, 112 mmol), Pd(dppf)Cl2.CH2Cl2 (5.92 g, 7.28 mmol) and K2CO3 (47.33 g, 343 mmol). The flask was flushed with nitrogen and then charged with sparged toluene (97 mL), sparged water (97 mL) and sparged DMF (61 mL). The reaction vessel was heated at 80° Celsius for 17 hours before cooling to room temperature. The reaction mixture was filtered and the filtrate was concentrated to dryness. The residue was extracted with EtOAc (200 mL×3), the combined extracts dried over MgSO4, filtered and concentrated to dryness. The residue was subjected to FCC to give the title compound (29.68 g). MS (ESI): mass calcd. for C16H16FN3O, 273.13; m/z found, 274.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.32-8.26 (dd, J=2.5, 1.5, 1H), 8.02-7.96 (d, J=1.5, 1H), 7.54-7.47 (m, 1H), 7.20-7.14 (m, 1H), 6.65 (s, 2H), 3.87-3.79 (d, J=1.0, 3H), 3.79-3.68 (m, 1H), 2.34-2.24 (m, 2H), 2.17-2.06 (m, 2H), 2.06-1.94 (m, 1H), 1.87-1.76 (m, 1H).

Workup

  1. additionTo a 1000 mL round-bottom flask were added a stir bar
  2. customThe flask was flushed with nitrogen
  3. additioncharged with sparged toluene (97 mL)
  4. customsparged water (97 mL)
  5. customsparged DMF (61 mL)
  6. temperaturebefore cooling to room temperature
  7. filtrationThe reaction mixture was filtered
  8. concentrationthe filtrate was concentrated to dryness
  9. extractionThe residue was extracted with EtOAc (200 mL×3)
  10. dry with materialthe combined extracts dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-b9de46adf62e4637a448a119192ab4be
Source dataset
uspto-grants-2015_07
Patent number
US09073876B2

Reaction notes

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