Potassium Carbonate → 5'-(3-Chlorophenyl)-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

HRID 1770961Notes

Reaction equation

HRID 1770961 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[CH:14][C:15]2[O:26][C:25]3([CH2:31][CH2:30][CH:29]([O:32][CH3:33])[CH2:28][CH2:27]3)[C:18]3([N:22]=[C:21]([NH2:23])[C:20]([CH3:24])=[N:19]3)[C:16]=2[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[CH:14][C:15]3[O:26][C:25]4([CH2:27][CH2:28][CH:29]([O:32][CH3:33])[CH2:30][CH2:31]4)[C:18]4([N:22]=[C:21]([NH2:23])[C:20]([CH3:24])=[N:19]4)[C:16]=3[CH:17]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine2×

Product 1

HCID 679793635'-(3-Chlorophenyl)-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amineYield 47%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

3-Chlorophenylboronic acid (47.7 mg, 0.31 mmol), 5′-bromo-4-methoxy-5″-methyldispiro-[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 77 mg, 0.20 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (8.37 mg, 10.18 μmol) were put in a microwave vial and dissolved in dry dioxane (2 mL). A 2 M aq. solution of K2CO3 (0.204 mL, 0.41 mmol) was added, the mixture was degassed with nitrogen gas and the mixture was heated at 120° C. for 20 min in a microwave reactor. The mixture was combined with a second reaction from 10 mg (0.03 mmol) of 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine and concentrated. EtOAc (7 mL) and a sat. aq. solution of NaHCO3 (5 mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (5 mL) and the combined organic layers were dried over MgSO4, filtered and evaporated. The crude product was purified by preparative chromatography, yielding 38.5 mg of the title compound (41% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.21 (m, 1H), 1.46 (m, 3H), 1.82 (m, 2H), 1.98 (m, 2H), 2.21 (s, 3H), 3.09 (m, 1H), 3.22 (s, 3H), 6.71 (br. s., 2H), 6.85 (d, 1H), 6.98 (d, 1H), 7.32 (m, 1H), 7.40 (s, 1H), 7.47 (m, 1H), 7.51 (m, 1H), 7.54 (s, 1H); MS (APCI+) m/z 410 [M+H]+.

Workup

  1. customthe mixture was degassed with nitrogen gas
  2. concentrationconcentrated
  3. additionEtOAc (7 mL) and a sat. aq. solution of NaHCO3 (5 mL) was added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with EtOAc (5 mL)
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by preparative chromatography

Sources & evidence

ORD record
ord-632a28c5f7184073af7b34c1ce686d99
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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