Triphenylphosphine → 6-isopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one

HRID 535476Notes

Reaction equation

HRID 535476 reaction equation
[N:1]1([CH2:7][CH2:8][N:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[N:16][C:17]([C:20]4[CH:21]=[C:22]([CH2:26]O)[CH:23]=[CH:24][CH:25]=4)=[N:18][CH:19]=3)[CH:11]=[N:10]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:28]([C:31]1[CH:32]=[CH:33][C:34](=[O:37])[NH:35][N:36]=1)([CH3:30])[CH3:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH:28]([C:31]1[CH:32]=[CH:33][C:34](=[O:37])[N:35]([CH2:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C:17]3[N:16]=[CH:15][C:14]([C:12]4[CH:11]=[N:10][N:9]([CH2:8][CH2:7][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[CH:13]=4)=[CH:19][N:18]=3)[CH:21]=2)[N:36]=1)([CH3:30])[CH3:29]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 230281476-Isopropyl-3-pyridazinoneHCID 58289705(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

Product 1

HCID 426416116-isopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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. temperatureis cooled in an ice bath
  2. customit is evaporated
  3. customThe residue is chromatographed on a silica-gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-db7e89d2ea604d20a389220af0982f78
Source dataset
uspto-grants-2014_10
Patent number
US08859547B2

Reaction notes

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