1,2-Dimethoxyethane → 2-Cyclopropyl-4-[6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-benzaldehyde

HRID 1851169Notes

Reaction equation

HRID 1851169 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][N:5]2[N:15]=[C:16](C3CC3)[N:17]=[C:4]2[N:3]=1.[CH:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22].[C:32](=O)([O-])[O-].[Na+].[Na+].CO[CH2:40][CH2:41]OC>O.ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:41]1([C:24]2[CH:25]=[C:26]([C:2]3[C:7]([C:8]4[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=4)=[CH:6][N:5]4[N:15]=[CH:16][N:17]=[C:4]4[N:3]=3)[CH:27]=[CH:28][C:23]=2[CH:21]=[O:22])[CH2:40][CH2:32]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 867030285-Chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine

Product 1

HCID 867030522-Cyclopropyl-4-[6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-benzaldehydeYield 31.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 3.57 g of the 5-chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine (60% pure) described in step 3 and 1.22 g (8.1 mmol) 4-formylphenylboronic acid in 25 mL 1,2-dimethoxyethane are added 273 mg (0.33 mmol) dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) and 14.5 mL of a sodium carbonate solution (10%). The resulting mixture was heated to 90° C. under an inert gas atmosphere for 20 h. The reaction mixture is diluted with 100 mL water and 250 mL dichloromethane. After vigorous stirring for one hour, the organic phase is separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers are washed with water and dried over sodium sulphate. The solvent is evaporated and the residue is purified by chromatography on silica gel (dichloromethane/methanol) to yield 1.68 g (31.6%) of the desired aldehyde contaminated with 2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine. Despite the impurity the aldehyde is used in the next reaction.

Workup

  1. customthe organic phase is separated
  2. extractionthe aqueous phase extracted twice with dichloromethane
  3. washThe combined organic layers are washed with water
  4. dry with materialdried over sodium sulphate
  5. customThe solvent is evaporated
  6. customthe residue is purified by chromatography on silica gel (dichloromethane/methanol)

Sources & evidence

ORD record
ord-bcbcd2940b574b388f07e087930642da
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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