Triethylamine → 6-phenoxy-2-(3-{5-[1-(2-pyrrolidin-1-ylethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one

HRID 2207256Notes

Reaction equation

HRID 2207256 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:9]=[C:10]([CH:26]=[CH:27][CH:28]=2)[CH2:11][N:12]2[C:17](=[O:18])[CH:16]=[CH:15][C:14]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:13]2)=[N:6][CH:7]=1.[N:29]1([CH2:34][CH2:35][N:36]2[CH:40]=[C:39](B3OC(C)(C)C(C)(C)O3)[CH:38]=[N:37]2)[CH2:33][CH2:32][CH2:31][CH2:30]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N(CC)CC)C>COCCOC.CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:19]([C:14]1[CH:15]=[CH:16][C:17](=[O:18])[N:12]([CH2:11][C:10]2[CH:26]=[CH:27][CH:28]=[C:8]([C:5]3[N:4]=[CH:3][C:2]([C:39]4[CH:38]=[N:37][N:36]([CH2:35][CH2:34][N:29]5[CH2:33][CH2:32][CH2:31][CH2:30]5)[CH:40]=4)=[CH:7][N:6]=3)[CH:9]=2)[N:13]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 18407952Tripotassium phosphate trihydrateHCID 584970712-[3-(5-bromopyrimidin-2-yl)benzyl]-6-phenoxy-2H-pyridazin-3-oneHCID 588858611-(2-(pyrrolidin-1-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 468365016-phenoxy-2-(3-{5-[1-(2-pyrrolidin-1-ylethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

3.5 A suspension of 218 mg (0.50 mmol) of 2-[3-(5-bromopyrimidin-2-yl)benzyl]-6-phenoxy-2H-pyridazin-3-one, 251 mg (0.75 mmol) of 1-(2-pyrrolidin-1-ylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (content 87%) and 230 mg (1.00 mmol) of tripotassium phosphate trihydrate in 2 ml of 1,2-dimethoxyethane and 1 ml of DMF is heated to 85° C. under nitrogen. 35.0 mg (0.05 mmol) of bis(triphenylphosphine)palladium(II) chloride and 9 μl (0.07 mmol) of triethylamine are then added and stirred at 85° C. for 42 hours. The reaction mixture is partitioned between THF and saturated sodium chloride solution. The organic phase is dried over sodium sulfate, evaporated and chromatographed on a silica-gel column with methanol/tert-butyl ether as eluent, giving 6-phenoxy-2-(3-{5-[1-(2-pyrrolidin-1-ylethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one as yellowish amorphous material; ESI 520.

Workup

  1. customThe reaction mixture is partitioned between THF and saturated sodium chloride solution
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. customevaporated
  4. customchromatographed on a silica-gel column with methanol/tert-butyl ether as eluent

Sources & evidence

ORD record
ord-9f5a11ab88e44154bc691ffc1efd2fbe
Source dataset
uspto-grants-2016_06
Patent number
US09376426B2

Reaction notes

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