Sodium Carbonate → 1-(1,1-Dimethyl-2-morpholin-4-yl-ethyl)-5-(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1,3-dihydro-benzoimidazol-2-one

HRID 1716382Notes

Reaction equation

HRID 1716382 reaction equation
[CH3:1][C:2]([N:11]1[C:15]2[CH:16]=[CH:17][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:19][C:14]=2[NH:13][C:12]1=[O:29])([CH3:10])[CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.Br[CH:31]=[C:32]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[CH2:36][O:35][C:34]2[CH:43]=[C:44]([F:47])[CH:45]=[CH:46][C:33]1=2.C([O-])([O-])=O.[Na+].[Na+].O.CCOC(C)=O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]([N:11]1[C:15]2[CH:16]=[CH:17][C:18]([CH:31]=[C:32]3[C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[CH2:36][O:35][C:34]4[CH:43]=[C:44]([F:47])[CH:45]=[CH:46][C:33]3=4)=[CH:19][C:14]=2[NH:13][C:12]1=[O:29])([CH3:10])[CH2:3][N:4]1[CH2:5][CH2:6][O:7][CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 22728543Water ethylacetateHCID 588114751-(1,1-Dimethyl-2-morpholin-4-yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-oneHCID 6733469611-Bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepine

Product 1

HCID 685112201-(1,1-Dimethyl-2-morpholin-4-yl-ethyl)-5-(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1,3-dihydro-benzoimidazol-2-oneYield 80%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Mix 1-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (900 mg of 60% purity, 1.34 mmol), 11-bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 520 mg, 1.7 mmol), 2N Na2CO3 (4 mmol) in dioxane (10 mL). Sparge with nitrogen for 10 min and then add tetrakistriphenylphosphine Pd (0) (98 mg, 0.08 mmol) and heat at 90-100° C. 5 days. Cool the reaction and shake with water/EtOAc. Dry (MgSO4) and concentrate to give 1.05 g crude product. Purify by column chromatography using 2% 2N NH3 in MeOH/methylene chloride to give 400 mg (80%) title compound as an off-white solid. MS (es) 500 (M+1), 498 (M−1); HPLC (ISO80-10M) t=1.95 min (100%); 1NMR (CDCl3) 8.17 (s, 1H), 7.49 (t, 1H, J=7.5 Hz), 7.46 (d, 1H, J=7.0 Hz), 7.37 (t, 1H, J=7.0 Hz), 7.26 (t, 1H, J=7.5 Hz), 7.14 (d, 1H, J=7.5 Hz), 6.91 (d, 1H, J=8.5 Hz), 6.89 (s, 1H), 6.81 (d, 1H, J=7.5 Hz), 6.70 (td, 1H, J=11.7, 4.1 Hz), 6.66 (s, 1H), 6.56 (dd, 1H, J=10.1, 2.6 Hz), 6.03-4.76 (br d, 2H), 3.85-3.70 (m, 6H), 2.73 (t, 4H, J=4.2 Hz), 1.13 (s, 6H).

Workup

  1. customSparge with nitrogen for 10 min
  2. custom5 days
  3. temperatureCool
  4. customthe reaction
  5. dry with materialDry (MgSO4)
  6. concentrationconcentrate
  7. customto give 1.05 g crude product
  8. customPurify by column chromatography

Sources & evidence

ORD record
ord-83297e86b447428c9703128c904644cb
Source dataset
uspto-grants-2010_09
Patent number
US07803814B2

Reaction notes

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