Sodium Carbonate → 5-(3,7-Difluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-one

HRID 2218768Notes

Reaction equation

HRID 2218768 reaction equation
Br[CH:2]=[C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([F:14])[C:8]=2[CH2:7][O:6][C:5]2[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:4]1=2.[N:20]1([CH2:26][CH2:27][N:28]2[C:32]3[CH:33]=[CH:34][C:35](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:31]=3[NH:30][C:29]2=[O:46])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.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:19][C:16]1[CH:17]=[CH:18][C:4]2[C:3](=[CH:2][C:35]3[CH:34]=[CH:33][C:32]4[N:28]([CH2:27][CH2:26][N:20]5[CH2:21][CH2:22][O:23][CH2:24][CH2:25]5)[C:29](=[O:46])[NH:30][C:31]=4[CH:36]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:14])[C:8]=3[CH2:7][O:6][C:5]=2[CH:15]=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 67334734HCID 67334734, compound

Product 1

HCID 688897545-(3,7-Difluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-oneYield 66.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Following procedures essentially as described in Example 219, mix 11-bromomethylene-3,7-difluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 200 mg, 0.619 mmol) (prepared essentially as described in Preparation 55), 1-(2-morpholin-4-yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (220 mg, 0.589 mmol), Na2CO3 (2M in water, 736 □L, 1.47 mmol), dioxane (4 mL), and Pd(PPh3)4 (36 mg, 0.031 mmol). Purify the crude product on silica gel (64 g) eluting with 2% (2M NH3/MeOH)/CH2Cl2 to afford 191 mg (66%) of the title compound as a white foam. HPLC (ISO80-10) t=1.95 min, 98%; MS [ES] 488 (M−H), 490 (M+H); 1H-NMR (DMSO-d6) δ 10.69 (s, 1H), 7.58 (dd, 1H, J=8.8, 7.0 Hz), 7.24 (m, 2H), 7.02 (s, 1H), 6.96 (d, 1H, J=8.4 Hz), 6.80 (m, 3H), 6.64 (m, 2H), 5.56-5.20 (br d, 2H), 3.81 (t, 2H, J=6.4 Hz), 3.46 (t, 4H, 4.4 Hz), 2.48 (m, 2H), 2.37 (s, 4H).

Workup

  1. customprepared essentially
  2. customPurify the crude product on silica gel (64 g)
  3. washeluting with 2% (2M NH3/MeOH)/CH2Cl2

Sources & evidence

ORD record
ord-4783a378ae4349d69934f242bd55af74
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

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