Dichloromethane → (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

HRID 535475Notes

Reaction equation

HRID 535475 reaction equation
O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:13]1[CH:14]=[N:15][C:16]([C:19]2[CH:20]=[C:21]([CH2:25][OH:26])[CH:22]=[CH:23][CH:24]=2)=[N:17][CH:18]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][N:38]([CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)[CH:39]=2)O1.ClCCl>COCCOC.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>[N:42]1([CH2:41][CH2:40][N:38]2[CH:39]=[C:35]([C:13]3[CH:14]=[N:15][C:16]([C:19]4[CH:20]=[C:21]([CH2:25][OH:26])[CH:22]=[CH:23][CH:24]=4)=[N:17][CH:18]=3)[CH:36]=[N:37]2)[CH2:43][CH2:44][O:45][CH2:46][CH2:47]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 18407952Tripotassium phosphate trihydrateHCID 59484879(3-(5-Bromopyrimidin-2-yl)phenyl)methanol

Product 1

HCID 58289705(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

7.2 4.25 g (20.0 mmol) of tripotassium phosphate trihydrate and 842 mg (1.2 mmol) of bis(triphenylphosphine)palladium chloride are added to a solution, kept under nitrogen, of 2.65 g (1.0.0 mol) of [3-(5-bromopyrimidin-2-yl)-phenyl]methanol and 3.38 g (11.0 mmol) of 4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethyl}morpholine in 50 ml of 1,2-dimethoxyethane, and the mixture is stirred at 80° C. for 18 hours. Dichloromethane and water are added to the reaction mixture, which is then filtered through kieselguhr, and the residue is washed with dichloromethane. The organic phase is separated off, dried over sodium sulfate and evaporated. The residue is recrystallised from 2-propanot, giving (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol as yellowish crystals; ESI 366. 7.3 A solution, kept under nitrogen, of 324 mg (0.70 mmol) of (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol, 131 mg (0.91 mmol) of 6-isopropyl-2H-pyridazin-3-one and 278 mg (1.05 mmol) of triphenylphosphine in 1.4 ml of THF is cooled in an ice bath, and 217 μl (1.056 mmol) of diisopropyl azodicarboxylate are added dropwise. After the reaction mixture has been stirred at room temperature for 2 hours, it is evaporated. The residue is chromatographed on a silica-gel column with dichloromethane/methanol as eluent, giving 6-isopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one (“A13”) as yellowish crystals; ESI 486;

Workup

  1. filtrationis then filtered through kieselguhr
  2. washthe residue is washed with dichloromethane
  3. customThe organic phase is separated off
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe residue is recrystallised from 2-propanot

Sources & evidence

ORD record
ord-81cdc3d121364a8ca0aefdbe5a28bd84
Source dataset
uspto-grants-2014_10
Patent number
US08859547B2

Reaction notes

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