Sodium Carbonate → 5-(2,8-Difluoro-10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidenemethyl)-1-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-one

HRID 2218744Notes

Reaction equation

HRID 2218744 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][C:39]([F:41])=[CH:40][C:35]=2[CH2:34][CH2:33][C:32]2[CH:42]=[C:43]([F:46])[CH:44]=[CH:45][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:41][C:39]1[CH:38]=[CH:37][C:36]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:31]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:32]=3[CH2:33][CH2:34][C:35]=2[CH:40]=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 688911995-bromomethylene-2,8-difluoro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene

Product 1

HCID 597702555-(2,8-Difluoro-10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidenemethyl)-1-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-oneYield 45.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Following procedures essentially as described in Example 219, mix 1-(2-morpholin-4yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (520 mg, 1.4 mmol), 5-bromomethylene-2,8-difluoro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (510 mg, 1.6 mmol)(prepared using a procedure essentially as described for the 2,8-dichloro derivative in Example 182), 2N Na2CO3 (1 mL), dioxane (10 mL) and (Ph3P)4Pd (67 mg, 0.06 mmol). Purify the crude product by column chromatography using MeOH/ethyl acetate to give 310 mg colorless oil that solidified upon drying, HPLC (ISO80-10M) t=2.03 (97%). MS (ES) 488 (M+1), 486 (M−1). H NMR 10.69 (s, 1H), 7.49 (dd, 1H, J=8.4, 6.2 Hz), 7.22 (dd, 1H, J=9.7, 2.2 Hz), 7.02 (td, 1H, J=12.0, 4.2 Hz), 6.97-6.83 (m, 4H), 6.81 (s, 1H), 6.72 (d, 1H, J=7.9 Hz), 6.56 (s, 1H), 3.80 (t, 2H, J=6.2 Hz), 3.47 (t, 4H, J=4.2 Hz), 3.31 (s, 2H), 2.90 (s, 2H), 2.48 (m, 2H), 2.38 (s, 4H).

Workup

  1. customprepared
  2. customPurify the crude product by column chromatography

Sources & evidence

ORD record
ord-9ab26fbf5f0e40f9a5f07fb3af383d56
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

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