Toluene → 8-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

HRID 473216노트

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HRID 473216 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].[CH:24]1(B(O)O)[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O>[CH:24]1([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([C:12]([F:20])([F:21])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)[N:8]=[C:7]3[S:22][CH3:23])[CH2:26][CH2:25]1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

생성물 1

HCID 666098168-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline수율 84%

시약·촉매·용매 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)촉매HCID 962Water용매

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온도
100 °C

실험 절차

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (200 mg, 0.5 mmol), dichlorobis(tricyclohexylphosphine)palladium(II) (37 mg, 0.05 mmol), cyclopropylboronic acid (65 mg, 0.75 mmol) and K3PO4 (371 mg, 1.75 mmol) were added toluene (6 mL) and water (0.5 mL). The reaction vessel was evacuated and flushed with argon (3×), and then the mixture was heated at 100° C. for 4 h. The mixture was concentrated under reduced pressure onto Celite and the residue was purified by silica gel chromatography eluting with 10-50% EtOAc/hexanes to afford impure 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (150 mg, 84%) which was used without further purification.

후처리

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (3×)
  3. concentrationThe mixture was concentrated under reduced pressure onto Celite
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with 10-50% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-4b691892610748fdaab7fcdc1a140446
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633207B2

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