Potassium Phosphate, Tribasic → (S)-3-chloro-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455630노트

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HRID 455630 반응식
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12]([Cl:22])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[F:23][C:24]1[C:29](B(O)O)=[CH:28][CH:27]=[CH:26][N:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[Cl:22][C:12]1[N:11]=[CH:10][C:9]2[O:8][C:5]3[C:4]([C@:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:14]=2[CH:13]=1)=[CH:3][C:2]([C:29]1[C:24]([F:23])=[N:25][CH:26]=[CH:27][CH:28]=1)=[CH:7][CH:6]=3

참가 물질

4

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 58465879(S)-7-bromo-3-chloro-2',6'-dihydrospiro[chromeno [2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

생성물 1

HCID 86658381(S)-3-chloro-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine수율 95%

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온도
90 °C

실험 절차

A vial was charged with (S)-7-bromo-3-chloro-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (546.36 mg, 1.435 mmol), 2-fluoropyridin-3-ylboronic acid (303 mg, 2.153 mmol), potassium phosphate (914 mg, 4.31 mmol), and bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (50.8 mg, 0.072 mmol). The vial was flushed with Argon, and then dioxane (5383 μL) and water (1794 μL) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 20 min at 90° C. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, concentrated under reduced pressure. The residue was purified by chromatography (0-100% EtOAc/Hexane) to give (S)-3-chloro-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (510.4 mg, 95% purity) as an off-white solid.

후처리

  1. customThe vial was flushed with Argon
  2. additiondioxane (5383 μL) and water (1794 μL) were added
  3. customThe vial was sealed
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography (0-100% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-45d3f2c92551496fbc08dbbb5e3801fa
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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