Tetrahydrofuran → HCID 49855156, compound

HRID 1503131Notes

Reaction equation

HRID 1503131 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2/[C:11](=[CH:14]/[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)/[C:12]#[N:13].C1COCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:34][O:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43]>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].C(OCC)C>[N:17]1[CH:18]=[CH:19][CH:20]=[C:15](/[CH:14]=[C:11](/[C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:38]4[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:36]([O:35][CH3:34])[CH:37]=4)[CH:3]=3)[NH:7][CH:6]=2)\[C:12]#[N:13])[CH:16]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 49855157HCID 49855157, compound

Product 1

HCID 49855156HCID 49855156, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (Z)-2-(5-bromo-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile (180 mg, 0.56 mmol, 1.0 eq.) in anhydrous and degazed THF (6.0 mL) were added, under an argon atmosphere, K3PO4 (236 mg, 1.11 mmol, 2.0 eq.), PdCl2(dppf)*CH2Cl2 (41 mg, 0.056 mmol, 0.1 eq.) and 3,4,5-trimethoxyphenylboronic acid (235 mg, 1.11 mmol, 2.0 eq.). The reaction apparatus was protected from light and the mixture was heated at 50° C. for 16 hours, and then, quenched with a saturated aqueous ammonium chloride solution, after cooling to room temperature. The mixture was extracted with ethyl acetate and the organic layer was washed with water, dried over MgSO4, and then, evaporated under reduced pressure. The residue was purified by silica gel flash-column chromatography (eluent: heptane/AcOEt, 40/60 to 30/70) to afford, after trituration with diethyl ether, the compound (38) as a yellow solid (145 mg, 63%). IR νmax (cm−1): 2216 (νCN), 3307 (νN—H); 1H NMR (DMSO, 500 MHz) δ (ppm): 3.70 (3H, s, 11′-methoxy), 3.88 (6H, s, 10′- and 12′-methoxy), 6.96 (2H, s, H9′ and H13′), 7.55 (3H, m, H6′, H7′ and H5″), 7.88 (1H, m, H4′), 7.93 (1H, s, H3), 8.24 (1H, s, H2′), 8.35 (1H, d, J4″-5″=7.9 Hz, H4″), 8.59 (1H, d, J6-5″=4.9 Hz, H6″), 9.01 (1H, s, H2″), 11.84 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 56.5 (10′- and 12′-methoxy), 60.5 (11′-methoxy), 105.3 (C9′ and C13′), 108.4 (C2), 111.4 (C3′), 113.2 (C7′), 118.2 (C2′), 118.6 (C1), 122.9 (C6′), 124.1 (C5″), 124.5 (C3a′), 128.4 (C4′), 131.4 (C3″), 133.6 (C11′), 134.2 (C7a′), 135.2 (C4″), 137.2 (C3), 138.0 (C8′), 150.1 (C6″), 150.5 (C2″), 153.6 (C10′ and C12′); ESI-MS: m/z 412.2 ([M+H]+), 434.1 ([M+Na]+); HRESI-MS: m/z 434.1481 (calcd for C25H21N3O3Na+, 434.1481).

Workup

  1. customquenched with a saturated aqueous ammonium chloride solution
  2. temperatureafter cooling to room temperature
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel flash-column chromatography (eluent: heptane/AcOEt, 40/60 to 30/70)
  8. customto afford

Sources & evidence

ORD record
ord-a75baf1fe47d42b4b9970a8602d3d460
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

Loading…