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

HRID 455645노트

반응식

HRID 455645 반응식
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.[F:37][C:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[CH:40][N:39]=1.C(=O)([O-])[O-].[K+].[K+]>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].C(Cl)Cl.O1CCOCC1>[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]([C:42]2[CH:41]=[CH:40][N:39]=[C:38]([F:37])[CH:43]=2)[CH:8]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 867619685-Amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthene]-7'-yl trifluoromethanesulfonate

생성물 1

HCID 533903114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine수율 85%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
85 °C

실험 절차

A 10 ml resealable tube was charged with 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (385 mg, 0.730 mmol), 2-fluoropyridin-4-ylboronic acid (165 mg, 1.168 mmol), PdCl2(dppf)-DCM adduct (59.6 mg, 0.073 mmol), dioxane (3650 pt) and potassium carbonate (1M solution) (2190 μL, 2.190 mmol). The mixture was flushed with argon, sealed and heated at 85° C. for 1 hr. The mixture was diluted with EtOAc, organic layer was filtered through Celite and concentrated. The brown residue was purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM) to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (294 mg, 85% yield) as off-white solid.

후처리

  1. customThe mixture was flushed with argon
  2. customsealed
  3. additionThe mixture was diluted with EtOAc, organic layer
  4. filtrationwas filtered through Celite
  5. concentrationconcentrated
  6. customThe brown residue was purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM)

출처 및 근거

ORD 기록
ord-471eca44146049348c47147e85ba946b
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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