Nitrogen → (4S,5S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9'-xanthen]-2-amine

HRID 335979

反応式

HRID 335979 の反応式
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[CH:4][N:3]=1.Br[C:12]1[CH:25]=[C:24]2[C:15]([O:16][C:17]3[C:18]([F:36])=[CH:19][C:20]([O:34][CH3:35])=[CH:21][C:22]=3[C:23]32[CH:29]([CH2:30][O:31][CH3:32])[S:28][C:27]([NH2:33])=[N:26]3)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].N#N.CC(N)CC1C=CC=CC=1.OP(O)(O)=O>O1CCOCC1.O>[F:36][C:18]1[C:17]2[O:16][C:15]3[C:24](=[CH:25][C:12]([C:7]4[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[CH:13][CH:14]=3)[C@@:23]3([C@@H:29]([CH2:30][O:31][CH3:32])[S:28][C:27]([NH2:33])=[N:26]3)[C:22]=2[CH:21]=[C:20]([O:34][CH3:35])[CH:19]=1

参加物

8

反応物 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 27832702-Fluoropyridine-3-boronic acidHCID 673829367'-bromo-4'-fluoro-2'-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9'-xanthen]-2-amine

生成物 1

HCID 67437807(4S,5S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9'-xanthen]-2-amine収率 59.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a sealed vessel was charge with (2-fluoropyridin-3-yl)boronic acid (1.543 g, 10.95 mmol), 7′-bromo-4′-fluoro-2′-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9′-xanthen]-2-amine (1.34 g, 3.04 mmol, prepared as in Method CC25), potassium carbonate (1.5M in water) (6.08 mL, 9.12 mmol) in dioxane (15 mL). It was purged with N2 and finally AmPHOS (0.13 g, 0.18 mmol) was added. The mixture was heated in oil bath at 100° C. for 20 min. The reaction mixture was allowed to cool to rt. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as an orange oil. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a gold Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 30% to 50% to 75% DCM/MeOH/NH4OH in 40% EtOAc in heptane, to provide (4S,5S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9′-xanthen]-2-amine (817 mg, 1.80 mmol, 59% yield) as light brown foam.

後処理

  1. additionwas added
  2. temperatureto cool to rt
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as an orange oil
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a gold Redi-Sep pre-packed silica gel column (40 g)
  11. washeluting with a gradient of 30% to 50% to 75% DCM/MeOH/NH4OH in 40% EtOAc in heptane

出典と根拠

ORDレコード
ord-5b8f396f53134425856abe6e881ed0d5
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

関連ノート

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