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

HRID 455716노트

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HRID 455716 반응식
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[CH:12][N:11]=1.Br[C:20]1[CH:33]=[CH:32][C:31]2[O:30][C:29]3[C:24](=[CH:25][C:26]([C:34]4[CH:39]=[CH:38][N:37]=[C:36]([F:40])[CH:35]=4)=[CH:27][CH:28]=3)[C@@:23]3([N:45]=[C:44]([NH2:46])[CH2:43][O:42][CH2:41]3)[C:22]=2[CH:21]=1>O1CCOCC1.O.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>[F:9][C:10]1[C:15]([C:20]2[CH:33]=[CH:32][C:31]3[O:30][C:29]4[C:24](=[CH:25][C:26]([C:34]5[CH:39]=[CH:38][N:37]=[C:36]([F:40])[CH:35]=5)=[CH:27][CH:28]=4)[C@@:23]4([N:45]=[C:44]([NH2:46])[CH2:43][O:42][CH2:41]4)[C:22]=3[CH:21]=2)=[CH:14][CH:13]=[CH:12][N:11]=1

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 67438537(R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

생성물 1

HCID 58465971(R)-2'-(2-fluoropyridin-3-yl)-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine수율 68.5%

시약·촉매·용매 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

In a microwave vial, the potassium phosphate (0.071 g, 0.334 mmol), PdCl2(AmPhos)2 (7.88 mg, 0.011 mmol), 2-fluoropyridin-3-ylboronic acid (0.020 g, 0.139 mmol), and (R)-2′-bromo-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.049 g, 0.111 mmol) were suspended in dioxane (2 mL) and water (0.5 mL). Argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The mixture was concentrated, and the residue was diluted with brine (15 mL), and the aqueous phase was extracted with 5% MeOH-dcm (3×25 mL). The organics were combined, dried over sodium sulfate and concentrated. The residue was purified by chromatography (3.5%-4.5% MeOH/DCM) to afford (R)-2′-(2-fluoropyridin-3-yl)-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (35 mg, 0.076 mmol). MS (m/z) 457 (M+H)+.

후처리

  1. customwas sealed
  2. concentrationThe mixture was concentrated
  3. additionthe residue was diluted with brine (15 mL)
  4. extractionthe aqueous phase was extracted with 5% MeOH-dcm (3×25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (3.5%-4.5% MeOH/DCM)

출처 및 근거

ORD 기록
ord-268b999a275b45ebb52ae6f698650ce3
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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