Potassium tert-butoxide → 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(tetrahydro-2H-pyran-4-yl)vinyl)thiazolo[5,4-b]pyridine

HRID 1177531노트

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HRID 1177531 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]([CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=O)[N:16]=3)=[C:9]([F:30])[CH:8]=1.[CH3:31][Si](C[Mg]Cl)(C)C.CC(C)([O-])C.[K+]>C1COCC1>[O:3]1[CH2:4][CH2:5][CH2:6][O:1][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]([CH:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)=[CH2:31])[N:16]=3)=[C:9]([F:30])[CH:8]=1

참가 물질

5

반응물 3

HCID 23665647Potassium tert-butoxide2회HCID 67111426(2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridine-5-yl)(tetrahydro-2H-pyran-4-yl)methanoneHCID 178418680HCID 178418680, 화합물

생성물 1

HCID 671121362-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(tetrahydro-2H-pyran-4-yl)vinyl)thiazolo[5,4-b]pyridine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
0 °C

실험 절차

To a slurry of (2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridine-5-yl)(tetrahydro-2H-pyran-4-yl)methanone (0.408 g, 0.952 mmol) in 20 mL THF at ambient temp was added trimethylsilylmethylmagnesium chloride, 1.1 M solution in THF (1.472 mL, 1.619 mmol) dropwise via syringe. The reaction mixture became clear and dark brown. After 10 min, the reaction mixture became light orange and was cooled to 0° C. and was quenched by careful dropwise addition of sat'd aq NH4Cl. The reaction mixture was partitioned between satd NH4Cl and DCM. The aqueous layer was extracted with DCM 3 times, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give an orange solid. The crude was taken up in 10 mL THF and potassium tert-butoxide (0.128 g, 1.143 mmol) was added. The reaction mixture became dark brown. After 2 h, additional potassium tert-butoxide (0.128 g, 1.143 mmol) was added. After 2 h, the reaction mixture was partitioned between sat'd aq. NH4Cl and DCM. The aqueous layer was extracted with DCM, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The solid was suspended in a minimum amount of MeOH and filtered, rinsing with MeOH to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(tetrahydro-2H-pyran-4-yl)vinyl)thiazolo[5,4-b]pyridine as a white solid. MS (ESI) m/z: Calculated: 426.1; Observed: 427.1 (M++1).

후처리

  1. customwas quenched by careful dropwise addition of sat'd aq NH4Cl
  2. customThe reaction mixture was partitioned between satd NH4Cl and DCM
  3. extractionThe aqueous layer was extracted with DCM 3 times
  4. dry with materialthe combined organics were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an orange solid
  8. waitAfter 2 h
  9. waitAfter 2 h
  10. customthe reaction mixture was partitioned between sat'd aq. NH4Cl and DCM
  11. extractionThe aqueous layer was extracted with DCM
  12. dry with materialthe combined organics were dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. filtrationfiltered
  16. washrinsing with MeOH

출처 및 근거

ORD 기록
ord-95a248d0292c41c3bb2909937e9a1428
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842685B2

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