Potassium Carbonate → 4'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455640ノート

反応式

HRID 455640 の反応式
Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C:13]32[N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)=[CH:4][CH:3]=1.[F:25][C:26]1[C:31](B(O)O)=[CH:30][CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[F:24][C:8]1[C:7]2[O:6][C:5]3[C:14](=[CH:15][C:2]([C:31]4[C:26]([F:25])=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:3][CH:4]=3)[C:13]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:12]=2[CH:11]=[C:10]([O:22][CH3:23])[CH:9]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 584659217'-Bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

生成物 1

HCID 674375114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine収率 74.2%

試薬・触媒・溶媒 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

A 250 ml RBF was charged with 7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.73 g, 6.94 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.492 g, 0.694 mmol) and 2-fluoropyridin-3-ylboronic acid (1.467 g, 10.41 mmol). Dioxane (40 mL) and potassium carbonate (1M in water; 20.83 mL, 20.83 mmol) were added and the mixture was flushed with argon and heated at 85° C. for 30 minutes. The mixture was cooled to RT, diluted with EtOAc and the organic layer was separated and concentrated in vacuo to give a yellow residue. After triturating with 10 ml of ethanol the solid was filtered off, washed with EtOH (2×1 ml) and dried on air overnight to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.11 g, 5.15 mmol).

後処理

  1. customthe mixture was flushed with argon
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with EtOAc
  4. customthe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customto give a yellow residue
  7. customAfter triturating with 10 ml of ethanol the solid
  8. filtrationwas filtered off
  9. washwashed with EtOH (2×1 ml)
  10. customdried on air overnight

出典と根拠

ORDレコード
ord-615b58780a4c450fafb18687b9c316c7
出典データセット
uspto-grants-2013_07
特許番号
US08497264B2

反応ノート

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