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

HRID 2218761Notes

Reaction equation

HRID 2218761 reaction equation
N1([CH:7]([CH3:28])[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])CCOCC1.Br[CH:30]=[C:31]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[CH2:35][O:34][C:33]2[CH:42]=[C:43]([F:46])[CH:44]=[CH:45][C:32]1=2.[C:47]([O-:50])([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:46][C:43]1[CH:44]=[CH:45][C:32]2[C:31](=[CH:30][C:16]3[CH:15]=[CH:14][C:13]4[N:9]([CH2:8][CH2:7][CH2:28][N:9]5[CH2:10][CH2:47][O:50][CH2:7][CH2:8]5)[C:10](=[O:27])[NH:11][C:12]=4[CH:17]=3)[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[CH2:35][O:34][C:33]=2[CH:42]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6733469611-Bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepineHCID 688871091-(2-Morpholin-4-yl-propyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one

Product 1

HCID 688878615-(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-(3-morpholin-4-yl-propyl)-1,3-dihydro-benzoimidazol-2-one

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-propyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (205 mg, 0.53 mmol)(prepared following procedures essentially as described in Preparation 36), 11-bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 150 mg, 0.5 mmol), 2N Na2CO3 (0.5 mL), dioxane (5 mL) and (Ph3P)4Pd (53 mg, 0.046 mmol). Purify the crude product by column chromatography using 2N NH3 in MeOH/dichloromethane. Triturate the product obtained (192 mg) with hexane to give 170 mg pure title compound, HPLC (ISO80-10M) t=1.72 (100%). MS (ES) 486 (M+1), 484 (M−1). H NMR (DMSO-d6)10.68 (s, 1H), 7.57 (m, 2H), 7.35 (t, 1H, J=7.5 Hz), 7.22 (t, 1H, J=7.7 Hz), 6.96 (m, 3H), 6.78 (td, 1H, J=12.0, 4.2 Hz), 6.71 (d, 1H, J=7.5 Hz), 6.60 (m, 2H), 5.31 (br d, 2H), 3.72 (t, 2H, J=6.6 Hz), 3.46 (t, 4H, J=4.2 Hz), 2.48 (m, 4H), 1.71 (m, 2H), 2.20 (m, 6H).

Workup

  1. customprepared
  2. customPurify the crude product by column chromatography
  3. customTriturate the product
  4. customobtained (192 mg) with hexane

Sources & evidence

ORD record
ord-f82756ddfb6a4e5c9bdd7c60afabdf77
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

Loading…