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

HRID 241164Notes

Reaction equation

HRID 241164 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-6b84869606f64e74981e8735c46872be
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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