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

HRID 455650노트

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HRID 455650 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]([O:22][CH3:23])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[F:24][C:25]1[C:30](B(O)O)=[CH:29][CH:28]=[CH:27][N:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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:24][C:25]1[C:30]([C:2]2[CH:3]=[C:4]3[C@:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:14]4[CH:13]=[C:12]([O:22][CH3:23])[N:11]=[CH:10][C:9]=4[O:8][C:5]3=[CH:6][CH:7]=2)=[CH:29][CH:28]=[CH:27][N:26]=1

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 58465867(S)-7-bromo-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

생성물 1

HCID 67440000(S)-7-(2-fluoropyridin-3-yl)-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine수율 95.8%

시약·촉매·용매 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매

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온도
100 °C

실험 절차

A microwave vial was charged with (S)-7-bromo-3-methoxy-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.065 g, 0.173 mmol), 2-fluoropyridin-3-ylboronic acid (0.049 g, 0.346 mmol), potassium phosphate (0.110 g, 0.518 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.12 mg, 8.64 μmol). The vial was flushed with Ar (g), dioxane (0.648 mL) and water (0.216 mL) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 100° C. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (0-10% MeOH/EtOAc) to afford 65 mg of (S)-7-(2-fluoropyridin-3-yl)-3-methoxy-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a light yellow solid.

후처리

  1. customThe vial was flushed with Ar (g), dioxane (0.648 mL) and water (0.216 mL)
  2. additionwere added in sequence
  3. customThe vial was sealed
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified via column chromatography (0-10% MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-3bf688708ca644ec842c7ac1778c84e5
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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