Cesium carbonate → HCID 49833688, compound

HRID 473910Notes

Reaction equation

HRID 473910 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([CH:20]([F:22])[F:21])[CH2:16][CH2:15]3)=[O:13])[CH2:7][C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][C:35]([C:38]3[NH:39][CH:40]=[CH:41][N:42]=3)=[CH:34][CH:33]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[F:21][CH:20]([F:22])[CH:17]1[CH2:18][CH2:19][N:14]([C:12]([N:8]2[CH2:7][C:6]3[CH:23]=[C:2]([C:32]4[CH:37]=[CH:36][C:35]([C:38]5[NH:42][CH:41]=[CH:40][N:39]=5)=[CH:34][CH:33]=4)[CH:3]=[CH:4][C:5]=3[O:11][CH2:10][CH2:9]2)=[O:13])[CH2:15][CH2:16]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 596196622-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazoleHCID 67514013HCID 67514013, compound

Product 1

HCID 49833688HCID 49833688, compoundYield 4.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-bromo-4-{[4-(difluoromethyl)piperidine-1-yl]carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepine (78 mg, 0.20 mmol) (example 2, step 3), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazole (0.20 mmol), cesium carbonate (325 mg, 1.00 mmol), and dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (16 mg, 0.02 mmol) in dioxane (5.0 mL) and water (0.5 mL) was degassed with nitrogen, and then stirred at 90° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through celite. The filtrate was washed with water (1×) and brine (1×), dried over sodium sulfate, filtered and concentrated. Purification by preparative reverse phase HPLC (0.1% aqueous trifluoroacetic acid-acetonitrile) provided the title compound (4 mg, 4% yield). 1H NMR (400 MHz, methanol-d4): 7.97 (d, 2H), 7.91 (d, 2H), 7.66 (s, 2H), 7.62 (d, 1H), 7.57 (dd, 1H), 7.08 (d, 1H), 5.72 (m, 1H), 4.53 (s, 2H), 4.24 (m, 2H), 3.72 (m, 4H), 2.84 (m, 2H), 2.00 (m, 1H), 1.76 (m, 2H), 1.49 (m, 2H); MS (EI) for C25H26F2N4O2: 453 (MH+).

Workup

  1. customwas degassed with nitrogen
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through celite
  5. washThe filtrate was washed with water (1×) and brine (1×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by preparative reverse phase HPLC (0.1% aqueous trifluoroacetic acid-acetonitrile)

Sources & evidence

ORD record
ord-cc56bdb9240548099d5340fad8ed61a1
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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