Dichloromethane → HCID 90311095, compound

HRID 1519155Notes

Reaction equation

HRID 1519155 reaction equation
[Si]([O:8][C:9]1[C:10]([F:22])=[C:11](B(O)O)[CH:12]=[CH:13][C:14]=1[CH:15]1[CH2:18][CH2:17][CH2:16]1)(C(C)(C)C)(C)C.[NH2:23][C:24]1[CH:29]=[N:28][C:27](Br)=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>O.CN(C=O)C.C1(C)C=CC=CC=1>[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:11]2[C:10]([F:22])=[C:9]([OH:8])[C:14]([CH:15]3[CH2:16][CH2:17][CH2:18]3)=[CH:13][CH:12]=2)=[N:28][CH:29]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 90310649HCID 90310649, compound

Product 1

HCID 90311095HCID 90311095, compoundYield 87.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A 50 mL three-neck flask, equipped with a stir bar, nitrogen inlet and temperature probe, was charged with (3-((tert-butyldimethylsilyl)oxy)-4-cyclobutyl-2-fluorophenyl)boronic acid (1.7 g, 5.3 mmol), toluene (4.7 mL), DMF (2.8 mL) and water (4.7 mL). The solvent mixture was sparged for 30 minutes and then treated with 2-amino-5-bromopyrazine (923 mg, 5.3 mmol), potassium carbonate (2.19 g, 15.8 mmol) and dichloro[1,1′-bis(diphenyl-phosphino)ferrocene]palladium(II).CH2Cl2 (137 mg, 0.17 mmol). The reaction mixture was heated at 80° Celsius for 24 hours. The reaction mixture was then cooled to room temperature, diluted with water (8 mL) and the stirred for two hours. The precipitate was collected by filtration and dried in a vacuum oven at 60° Celsius overnight to give 3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenol (1.2 g, 87%). MS (ESI+) Calcd. for C14H14FN3O, 260.3; m/z found 260.1 [M+H]+. 1H NMR (400 MHz, DMSO), δ 8.24 (m, 1H), 7.98 (d, J=1.5 Hz, 1H), 7.09 (m, 1H), 7.00 (d, J=8.2 Hz, 1H), 6.57 (s, 2H), 3.81-3.72 (m, 1H), 2.34-2.14 (m, 2H), 2.14-1.69 (m, 4H).

Workup

  1. customA 50 mL three-neck flask, equipped with a stir bar, nitrogen inlet
  2. customThe solvent mixture was sparged for 30 minutes
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. filtrationThe precipitate was collected by filtration
  5. customdried in a vacuum oven at 60° Celsius overnight

Sources & evidence

ORD record
ord-9ad74d6779894198bed9c9ff69d8ecbd
Source dataset
uspto-grants-2015_07
Patent number
US09073876B2

Reaction notes

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