Morpholine → Racemic 4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-morpholino-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455642ノート

反応式

HRID 455642 の反応式
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:16][C:17]=3[C:18]32[N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]3)=[C:9]([F:34])[CH:8]=1)(=O)=O.BrC1C=C2[C:51]3([N:56]=[C:55](N)[CH2:54][O:53][CH2:52]3)C3C=C(Cl)N=CC=3OC2=CC=1.N1CCOCC1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:34][C:9]1[C:10]2[O:11][C:12]3[C:17](=[CH:16][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:14][CH:13]=3)[C:18]3([N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]3)[C:19]=2[CH:20]=[C:7]([N:56]2[CH2:51][CH2:52][O:53][CH2:54][CH2:55]2)[CH:8]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 584659017-Bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineHCID 867619685-Amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthene]-7'-yl trifluoromethanesulfonate

生成物 1

HCID 67439029Racemic 4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-morpholino-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine収率 550%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A re-sealable vial was charged with 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (200 mg, 0.379 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-isopropoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) 1 (27.6 mg, 0.038 mmol) and 0.5 ml of THF. The mixture was stirred at RT until all solids were dissolved. Morpholine (66.1 μL, 0.758 mmol) and LiHMDS (1M in THF) (1138 pt, 1.138 mmol) were added and the vial was sealed and stirred at RT for 20 minutes. The reaction was quenched by addition of water (1 ml) and diluted with EtOAc (2 ml). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×2 ml). The combined organic fractions were concentrated and purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM) to provide racemic 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholino-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (97 mg, 0.209 mmol, 55.1% yield).

後処理

  1. dissolutionwere dissolved
  2. customthe vial was sealed
  3. stirringstirred at RT for 20 minutes
  4. customThe reaction was quenched by addition of water (1 ml)
  5. additiondiluted with EtOAc (2 ml)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×2 ml)
  8. concentrationThe combined organic fractions were concentrated
  9. custompurified by chromatography (10-80% DCM/MeOH/NH4OH in DCM)

出典と根拠

ORDレコード
ord-7248f8aa93b54b7fa1bf43961d2878f4
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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