Ethanol → 4-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amine

HRID 1965117Notes

Reaction equation

HRID 1965117 reaction equation
[C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:20]1[CH:21]=[CH:22][C:23]2[O:34][C:33]3([CH2:39][CH2:38][CH:37]([O:40][CH3:41])[CH2:36][CH2:35]3)[C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]=2[CH:25]=1.CCO>COCCOC.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].O>[CH3:41][O:40][CH:37]1[CH2:38][CH2:39][C:33]2([C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]3[CH:25]=[C:20]([C:6]4[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=4)[CH:21]=[CH:22][C:23]=3[O:34]2)[CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 574164825-(1-Propynyl)pyridine-3-boronic Acid (contains varying amounts of Anhydride)2×HCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

Product 1

HCID 679793924-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amineYield 42%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-(Prop-1-ynyl)pyridin-3-ylboronic acid (Intermediate 15, 57.4 mg, 0.36 mmol), (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (9.79 mg, 0.01 mmol), cesium carbonate (233 mg, 0.71 mmol) and 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 90 mg, 0.24 mmol) were dissolved in a 6:3:1 mixture of DME:EtOH:water (2 mL) and heated at 150° C. in a microwave reactor for 15 min. The mixture was concentrated and the residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL). The layers were separated and the organic layer was dried over MgSO4 and concentrated. Purification of the crude product by preparative chromatography afforded 41 mg of the title compound (42% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.22 (m, 1 H), 1.46 (m, 3 H), 1.81 (m, 2 H), 1.98 (m, 2 H), 2.09 (s, 3 H), 2.21 (s, 3 H), 3.10 (m, 1 H), 3.22 (s, 3 H), 6.70 (s, 2 H), 6.95 (d, 1 H), 6.99 (d, 1 H), 7.56 (d, 1 H), 7.91 (t, 1 H), 8.47 (d, 1 H), 8.67 (d, 1 H); MS (APCI+) m/z 415 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL)
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude product by preparative chromatography

Sources & evidence

ORD record
ord-3be104eb4ae14cec8d0f470982021b19
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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