Sodium Carbonate → HCID 59272478, 화합물

HRID 558154노트

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HRID 558154 반응식
[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20](B5OC(C)(C)C(C)(C)O5)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:33])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1.Br[C:35]1[CH:36]=[C:37]([F:44])[CH:38]=[C:39]2[C:43]=1[NH:42][CH:41]=[CH:40]2.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+].[F-].[Cs+]>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].O.CS(C)=O.O1CCOCC1.CN(C=O)C>[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:35]5[CH:36]=[C:37]([F:44])[CH:38]=[C:39]6[C:43]=5[NH:42][CH:41]=[CH:40]6)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:33])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1

참가 물질

12

반응물 6

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 38528797-bromo-5-fluoro-1H-indoleHCID 17749109Barium hydroxide, octahydrateHCID 66738069HCID 66738069, 화합물

생성물 1

HCID 59272478HCID 59272478, 화합물수율 43.1%

시약·촉매·용매 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

Combine N-(2-(1H-1,2,3-triazol-1-yl)ethyl)-5-fluoro-4-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)pyrimidin-2-amine (0.12 g, 0.26 mmol), 7-bromo-5-fluoro-1H-indole (64 mg, 0.28 mmol, synthesized based on reference: Manfred S.; Assunta G.: Frédéric L., Eur. J. Org. Chem. 2006, 2956-2069), barium hydroxide octahydrate (0.24 g, 0.77 mmol, alternatively sodium carbonate, potassium carbonate, cesium fluoride), Pd(dppf)Cl2 (20 mg, 0.03 mmol) in 2 mL of mixed solvent of DMF (alternatively dioxane, DMSO) and water (4/1, v/v). Purge the mixture with N2 three times. Heat the reaction mixture to 80° C. for 4 h (HPLC monitor) (or microwave reactor). Cool to RT. Dilute with chloroform/IPA (3:1, v/v) 50 mL. Wash with water, aqueous saturated sodium chloride and dry over magnesium sulfate. Remove the organic solvent to give the crude product. Purify the residue by column chromatography (hexane to ethyl acetate, or methylene chloride and methanol) to give the title compound (0.053 g, 43%). MS (ES) m/z 474 [M+1]+.

후처리

  1. customPurge the mixture with N2 three times
  2. temperatureCool to RT
  3. additionDilute with chloroform/IPA (3:1
  4. washWash with water, aqueous saturated sodium chloride
  5. dry with materialdry over magnesium sulfate
  6. customRemove the organic solvent
  7. customto give the crude product
  8. customPurify the residue by column chromatography (hexane to ethyl acetate, or methylene chloride and methanol)

출처 및 근거

ORD 기록
ord-e17a4f135a9e4fbcb4abdc1921746228
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063035B2

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