Potassium Carbonate → 7-(1-Methyl-1H-indazol-5-yl)-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241164노트

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HRID 241164 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[CH:14][CH:13]=3)[CH2:7][C:6]=2[CH:22]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[N:36]([CH3:40])[N:35]=[CH:34]3)O1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:40][N:36]1[C:37]2[C:33](=[CH:32][C:31]([C:2]3[CH:3]=[CH:4][C:5]4[O:11][CH2:10][CH2:9][N:8]([C:12]5[C:21]6[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=6)[N:15]=[CH:14][CH:13]=5)[CH2:7][C:6]=4[CH:22]=3)=[CH:39][CH:38]=2)[CH:34]=[N:35]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 469415731-Methylindazole-5-boronic acid pinacol esterHCID 668207827-Bromo-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine

생성물 1

HCID 573892587-(1-Methyl-1H-indazol-5-yl)-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine수율 10%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
100 °C

실험 절차

A mixture of 7-bromo-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine (206 mg, 0.58 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-methyl-1H-indazole (158 mg (0.58 mmol) (reagent preparation 50), potassium carbonate (320 mg, 2.32 mmol), and dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (50 mg, 0.06 mmol) in dimethoxyethane (4.0 mL) and water (1.0 mL) was degassed with nitrogen, and then stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The mixture was filtered through celite and then the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography on silica ((2S)-100% ethyl acetate in hexanes) afforded the title Compound (23 mg, 10% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): 8.63 d, 1H), 8.11 (s, 1H), 8.03 (m, 2H), 7.95 (d, 1H), 7.75 (m, 3H), 7.70 (m, 1H), 7.61 (dd, 1H), 7.51 (m, 1H), 7.11 (d, 1H), 7.02 (d, 1H), 4.61 (s, 2H), 4.39 (m, 2H), 4.09 (s, 3H), 3.84 (m, 2H); MS (EI) for C26H22N4O: 407 (MH+).

후처리

  1. customwas degassed with nitrogen
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between water and ethyl acetate
  4. filtrationThe mixture was filtered through celite
  5. customthe layers were separated
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-6b84869606f64e74981e8735c46872be
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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