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Cesium fluoride → 2-hydroxy-N,N-dimethyl-2-{5-[3-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-pyridin-3-yl}-acetamide

HRID 886637
ノート
印刷プレビュー

反応式

HRID 886637 の反応式
[OH:1][CH:2]([C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]2[CH:15]=[C:16]3[C:22](I)=[CH:21][N:20](COCC[Si](C)(C)C)[C:17]3=[N:18][CH:19]=2)[CH:13]=1)[C:3]([N:5]([CH3:7])[CH3:6])=[O:4].[CH3:32][N:33]1[C:37]([Sn](CCCC)(CCCC)CCCC)=[CH:36][C:35]([C:51]([F:54])([F:53])[F:52])=[N:34]1.[F-].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[Cu]I.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].CN(C=O)C>[OH:1][CH:2]([C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]2[CH:15]=[C:16]3[C:22]([C:37]4[N:33]([CH3:32])[N:34]=[C:35]([C:51]([F:54])([F:53])[F:52])[CH:36]=4)=[CH:21][NH:20][C:17]3=[N:18][CH:19]=2)[CH:13]=1)[C:3]([N:5]([CH3:7])[CH3:6])=[O:4]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 25953Cesium fluorideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 120567101-Methyl-5-(tributylstannyl)-3-(trifluoromethyl)-1H-pyrazoleHCID 598248902-hydroxy-2-{5-[3-iodo-1(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-N,N-dimethyl-acetamide

生成物 1

HCID 136014290
2-hydroxy-N,N-dimethyl-2-{5-[3-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-pyridin-3-yl}-acetamide
収率 8%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-hydroxy-2-{5-[3-iodo-1(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-N,N-dimethyl-acetamide (194 mg, 0.4 mmol), 1-methyl-5(tributylstannyl)3-(trifluoromethyl)-1H-pyrazole (186 mg, 0.4 mmol), CuI (7 mg, 0.04 mmol), CsF (107 mg, 0.7 mmol), dichlorobis(benzonitrile)palladium (II) (7 mg, 0.02 mmol), tri-t-butylphosphine 10% w/v in hexanes (10 μl, 0.04 mmol) and DMF were stirred at 100° C. under nitrogen overnight. The mixture was allowed to cool to room temperature and then extracted with ethyl acetate (2X). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. The material was purified using silica gel chromatography and a gradient of ethyl acetate and hexane. The purified product was treated with dichloromethane/trifluoroacetate acid (1 ml/1 ml) at room temperature for 2 hours. The solvents were removed under vacuum and the crude was stirred in dichloromethane/ethylenediamine (1 ml/1 ml) for 2 hours at room temperature. Again the solvents was removed under vacuum and the crude was dissolved in DMSO, filtered and purified by reverse phase HPLC, lyophilized afforded 2-hydroxy-N,N-dimethyl-2-{5-[3-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-pyridin-3-yl}-acetamide (13.2 mg, 8% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.80 (s, 3H), 2.94 (s, 3H), 5.56 (s, 1H), 5.80 (s, 1H), 7.08 (s, 1H), 7.98 (s, 1H), 8.04 (t, 1H), 8.26 (d, 1H), 8.50 (d, 1H), 8.58 (d, 1H), 8.88 (d, 1H), 12.40 (s, 1H). MS: m/z 445.0 (M+H+).

後処理

  1. extractionextracted with ethyl acetate (2X)
  2. extractionThe combined organic layers were extracted with brine
  3. dry with materialdried with Na2SO4
  4. customdecanted
  5. concentrationconcentrated to dryness
  6. customThe material was purified
  7. additionThe purified product was treated with dichloromethane/trifluoroacetate acid (1 ml/1 ml) at room temperature for 2 hours
  8. customThe solvents were removed under vacuum
  9. customAgain the solvents was removed under vacuum
  10. dissolutionthe crude was dissolved in DMSO
  11. filtrationfiltered
  12. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-5acc9d2791434031811e1820c80bed4d
出典データセット
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08242280B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート