Potassium Carbonate → HCID 57386412, compound

HRID 1770970Notes

Reaction equation

HRID 1770970 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:11]3([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]3)[CH2:10][CH:9]([CH:18]3[CH2:23][CH2:22][O:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[O:8][C:5]2=[CH:6][CH:7]=1.[Cl:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:3]=[C:4]2[C:11]3([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]3)[CH2:10][CH:9]([CH:18]3[CH2:23][CH2:22][O:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[O:8][C:5]2=[CH:6][CH:7]=1.[Cl:26][C:27]1[CH:32]=[C:31]([C:2]2[CH:3]=[C:4]3[C:11]4([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]4)[CH2:10][CH:9]([CH:18]4[CH2:23][CH2:22][O:21][C:20]([CH3:24])([CH3:25])[CH2:19]4)[O:8][C:5]3=[CH:6][CH:7]=2)[CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 57386411HCID 57386411, compound2×

Product 2

HCID 57386411HCID 57386411, compoundHCID 57386412HCID 57386412, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

6-Bromo-2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-5′-methylspiro[chroman-4,2′-imidazol]-4′-amine (Isomeric mixture 1 from Example 49 Step 4, 0.08 g, 0.20 mmol), 3-chlorophenylboronic acid (0.046 g, 0.30 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.015 g, 0.02 mmol), 2 M aq. K2CO3 solution (0.197 mL, 0.39 mmol) and 1,4-dioxane (1.5 mL) were mixed in a vial and heated in a microwave reactor at 130° C. for 20 min. When cooled to r.t. the mixture was diluted with DCM, washed with water and dried over Na2SO4. The filtrate was concentrated and the product purified by preparative chromatography to yield Isomeric mixture 1 of the title compound (30 mg, 35% yield): 1H NMR (500 MHz, CDCl3) δ ppm 1.28 (m, 7H), 1.48 (m, 3H), 1.64 (d, 1H), 1.91 (t, 1H), 2.11 (m, 1H), 2.40 (s, 3H), 2.51 (t, 1H), 3.74 (td, 1H), 3.85 (td, 1H), 4.48 (dd, 1H), 6.81 (d, 1H), 7.01 (d, 1H), 7.26 (m, 1H), 7.32 (d, 2H), 7.40 (m, 2H); MS (ES+) m/z 438 [M+H]+.

Workup

  1. temperatureWhen cooled to r.t. the mixture
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationThe filtrate was concentrated
  5. customthe product purified by preparative chromatography

Sources & evidence

ORD record
ord-c19dfd4a74a948c7bc18a2bca97d1077
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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