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

HRID 2218765Notes

Reaction equation

HRID 2218765 reaction equation
Br[CH:2]=[C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][O:6][C:5]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:4]1=2.[CH:19]([N:22]1[C:26]2[CH:27]=[CH:28][C:29](B(O)O)=[CH:30][C:25]=2[NH:24][C:23]1=[O:34])([CH3:21])[CH3:20].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:18][C:15]1[CH:16]=[CH:17][C:4]2[C:3](=[CH:2][C:29]3[CH:28]=[CH:27][C:26]4[N:22]([CH:19]([CH3:21])[CH3:20])[C:23](=[O:34])[NH:24][C:25]=4[CH:30]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[CH2:7][O:6][C:5]=2[CH:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6733469611-Bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepineHCID 688879901-isopropyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-boronic acid

Product 1

HCID 688908515-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-isopropyl-1,3-dihydro-benzoimidazol-2-oneYield 69.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Following procedures essentially as described in Example 219, mix 11-bromomethylene-3-fluoro-6,11-dihydro-dibenzo[b,e]oxepine (150 mg, 0.493 mmol), 1-isopropyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-boronic acid (103 mg, 0.468 mmol)(prepared according to Scheme IX by using isopropylamine in Step A), Na2CO3 (2M in water, 620 □L, 1.23 mmol), dioxane (4 mL), and Pd(PPh3)4 (29 mg, 0.025 mmol). Purify the crude product on silica gel (24 g), eluting with 25% to 50% THF/hexanes to afford 130 mg (69%) of the title compound as a yellow foam. HPLC (ISO80-10) t=3.86 min, 98%; MS [ES] 399 (M−H); 1H-NMR (CDCl3) δ 9.10 (s, 1H), 7.44 (m, 2H), 7.32 (t, 1H, J=7.5 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.11 (d, 1H, J=7.5 Hz), 6.93 (d, 1H, J=8.4 Hz), 6.86 (s, 1H), 6.75 (d, 1H, J=8.4 Hz), 6.69 (s, 1H), 6.66 (td, 1H, J=11.7, 4.1 Hz), 6.52 (dd, 1H, J=10.3, 2.4 Hz), 5.92-4.73 (m, 2H), 4.66 (m, 1H), 1.51 (d, 6H, J=7.0 Hz).

Workup

  1. customPurify the crude product on silica gel (24 g)
  2. washeluting with 25% to 50% THF/hexanes

Sources & evidence

ORD record
ord-12a8b541a95b4132a699eeeb3d3d69a7
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

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