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

HRID 1851169노트

반응식

HRID 1851169 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6344Dichloromethane용매

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온도
90 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-bcbcd2940b574b388f07e087930642da
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957064B2

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