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 455716ノート

反応式

HRID 455716 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-268b999a275b45ebb52ae6f698650ce3
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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