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Tetraethyltin → 2-(Difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline

HRID 473187
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HRID 473187 반응식
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:21])([F:20])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[N:8]=[C:7]2[S:22][CH3:23].[CH2:24]([Sn](CC)(CC)CC)[CH3:25].[Li+].[Cl-]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CN(C=O)C>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:9]1[N:8]=[C:7]([S:22][CH3:23])[C:6]2[C:11](=[C:2]([CH2:24][CH3:25])[CH:3]=[CH:4][CH:5]=2)[N:10]=1
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참가 물질

6

반응물 3

HCID 11704TetraethyltinHCID 433294Lithium ChlorideHCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

생성물 1

HCID 666095022-(Difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline수율 73.7%

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물
촉매
HCID 6228Dimethylformamide용매

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온도
135 °C

실험 절차

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (300 mg, 0.75 mmol), bis(tri-tert-butylphosphine)palladium (38 mg, 0.075 mmol), tetraethyltin (0.295 mL, 1.5 mmol), and LiCl (95 mg, 2.25 mmol) was added DMF (15 mL). The reaction vessel was evacuated and flushed with argon (2×). The mixture was then heated in a microwave synthesizer at 135° C. for 30 min. The mixture was partitioned between EtOAc and saturated aq sodium bicarbonate and the organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel chromatography eluting with 0-10% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline (193 mg, 73%) as a white solid. LC-MS (ESI) m/z 350 (M+H)+.

후처리

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (2×)
  3. customThe mixture was partitioned between EtOAc and saturated aq sodium bicarbonate
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure onto Celite
  8. customThe mixture was purified by silica gel chromatography
  9. washeluting with 0-10% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-ba75f8f51b434f6fb068a37afaaaf1d6
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08633207B2

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