Dichloromethane → HCID 90313799, compound

HRID 1523739Notes

Reaction equation

HRID 1523739 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([C:9]#[N:10])[C:5](Br)=[N:6][CH:7]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[C:14]([F:21])[CH:13]=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]>[NH2:1][C:2]1[N:3]=[C:4]([C:9]#[N:10])[C:5]([C:15]2[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=2[F:21])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 871716806-Amino-3-bromo-2-pyrazinecarbonitrile

Product 1

HCID 90313799HCID 90313799, compound

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 200 mL round-bottomed flask were added a stirbar, 5-amino-3-cyano-2-bromopyrazine (4.09 g, 20.5 mmol), 4-chloro-2-fluorophenylboronic acid (3.90 g, 22.4 mmol), Pd(dppf)Cl2.CH2Cl2 (839 mg, 1.03 mmol) and K2CO3 (8.36 g, 60.5 mmol). The flask was flushed with nitrogen and then charged with toluene (17.5 mL), water (17.5 mL) and DMF (10.5 mL), all of which were sparged with N2. The flask was heated at 80° Celsius for 19 hours before cooling to rt and adding MgSO4 until the mixture was a thick paste. The reaction mixture was then stirred with EtOAc and filtered through a thick pad of celite. The pad was rinsed with EtOAc until the filtrate was colorless. The filtrate was concentrated to dryness and subjected to FCC to give 6-amino-3-(4-chloro-2-fluorophenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C11H6ClFN4, 248.03; m/z found, 249.0 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.67-7.60 (m, 2H), 7.46 (dd, J=8.4, 2.0, 1H), 7.37 (s, 2H).

Workup

  1. customThe flask was flushed with nitrogen
  2. additioncharged with toluene (17.5 mL), water (17.5 mL) and DMF (10.5 mL)
  3. customall of which were sparged with N2
  4. temperaturebefore cooling to rt
  5. additionadding MgSO4 until the mixture
  6. filtrationfiltered through a thick pad of celite
  7. washThe pad was rinsed with EtOAc until the filtrate
  8. concentrationThe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-cba445e151dc482eb55db1ae506f4cb7
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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