Sodium Carbonate → HCID 59272478、化合物

HRID 558154ノート

反応式

HRID 558154 の反応式
[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

参加物

12

反応物 6

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

生成物 1

HCID 59272478HCID 59272478、化合物収率 43.1%

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-e17a4f135a9e4fbcb4abdc1921746228
出典データセット
uspto-grants-2011_11
特許番号
US08063035B2

反応ノート

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