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

HRID 2218763Notes

Reaction equation

HRID 2218763 reaction equation
[N:1]1([CH2:7][CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][C:16](B4OC(C)(C)C(C)(C)O4)=[CH:17][C:12]=3[NH:11][C:10]2=[O:27])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH:29]=[C:30]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[CH2:34][O:33][C:32]2[CH:41]=[C:42]([F:45])[CH:43]=[CH:44][C:31]1=2.C([O-])([O-])=O.[Na+].[Na+]>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.O1CCOCC1>[F:45][C:42]1[CH:43]=[CH:44][C:31]2[C:30](=[CH:29][C:16]3[CH:15]=[CH:14][C:13]4[N:9]([CH2:8][CH2:7][N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)[C:10](=[O:27])[NH:11][C:12]=4[CH:17]=3)[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[CH2:34][O:33][C:32]=2[CH:41]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 597700961-(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 688871105-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-oneYield 16.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Following procedures essentially as described in Example 219, mix 1-(2-morpholin-4-yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (300 mg, 1.03 mmol), 11-bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepine (E isomer, 330 mg, 1.08 mmol), 2N Na2CO3 (1.4 mL), dioxane (10 mL) and (Ph3P)4Pd (44 mg, 0.038 mmol). Purify the crude product by column chromatography using 40% THF/hexane to yield 80 mg title compound as a pale yellow powder. HPLC (ISO80-10M) t=1.84 (96%), MS (ES) 472 (M+1), 470 (M−1). H NMR (DMSO-d6)10.72 (s, 1H), 7.57 (m, 2H), 7.35 (t, 1H, J=7.5 Hz), 7.23 (t, 1H, J=7.5 Hz), 7.00 (d, 1H, J=7.5 Hz), 6.97 (s, 1H), 6.93 (d, 1H, J=8.4 Hz), 6.79 (td, 1H, J=11.9, 4.3 Hz), 6.73 (d, 1H, J=8.4 Hz), 6.60 (m, 2H), 5.82-4.79 (m, 2H), 3.80 (t, 2H, J=6.4 Hz), 3.46 (t, 4H, J=4.4 Hz), 2.48 (m, 2H), 2.38 (s, 4H).

Workup

  1. customPurify the crude product by column chromatography

Sources & evidence

ORD record
ord-e3026ddd53444b0a871a6300a6b421f8
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

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