Water → 2-[3-(5-aminopyrazin-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one

HRID 1408396Notes

Reaction equation

HRID 1408396 reaction equation
O.[F:2][C:3]1[CH:4]=[C:5]([C:10]2[CH:11]=[CH:12][C:13](=[O:32])[N:14]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)[N:15]=2)[CH:6]=[C:7]([F:9])[CH:8]=1.Br[C:34]1[N:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=1.C(=O)([O-])O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(#N)C>[NH2:40][C:37]1[N:38]=[CH:39][C:34]([C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=2)[CH2:16][N:14]2[C:13](=[O:32])[CH:12]=[CH:11][C:10]([C:5]3[CH:4]=[C:3]([F:2])[CH:8]=[C:7]([F:9])[CH:6]=3)=[N:15]2)=[N:35][CH:36]=1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 5995392-Amino-5-bromopyrazineHCID 594848326-(3,5-difluorophenyl)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]-2H-pyridazin-3-one

Product 1

HCID 594849352-[3-(5-aminopyrazin-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

5 ml of water and 5 ml of acetonitrile are added to 150 mg (0.35 mmol) of 6-(3,5-difluorophenyl)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzyl]-2H-pyridazin-3-one, 63 mg (0.35 mmol) of 5-bromopyrazin-2-ylamine and 167 mg (1.99 mmol) of sodium hydrogencarbonate, and the mixture is degassed a number of times. Under an argon atmosphere, 20 mg (0.017 mmol) of tetrakis(triphenylphosphine)palladium(0) are added, and the mixture is subsequently heated at 80° C. for 15 h with stirring. A further 20 mg (0.017 mmol) of tetrakis(triphenylphosphine)palladium(0) are subsequently added, and the mixture is stirred at 80° C. for a further 24 h. The hot suspension is filtered. The filtrate is concentrated to half. After cooling to room temperature, the resultant precipitate is filtered off with suction and washed with a little water. The residue is purified by means of preparative HPLC; yield: 21 mg of “A280”; HPLC: Rt=2.68 min (method C); LC-MS: 392 (M+H).

Workup

  1. customthe mixture is degassed a number of times
  2. stirringthe mixture is stirred at 80° C. for a further 24 h
  3. filtrationThe hot suspension is filtered
  4. concentrationThe filtrate is concentrated to half
  5. temperatureAfter cooling to room temperature
  6. filtrationthe resultant precipitate is filtered off with suction
  7. washwashed with a little water
  8. customThe residue is purified by means of preparative HPLC

Sources & evidence

ORD record
ord-81e856607f8b4aa79def945904dae98b
Source dataset
uspto-grants-2014_12
Patent number
US08921357B2

Reaction notes

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