Dichloromethane → HCID 49855063, compound

HRID 1503132Notes

Reaction equation

HRID 1503132 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].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[F:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>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.C1COCC1>[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3/[C:11](=[CH:14]/[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)/[C:12]#[N:13])=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 49855157HCID 49855157, compound

Product 1

HCID 49855063HCID 49855063, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

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 4-fluorophenylboronic acid (155 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, 50/50 to 30/70) to afford, after trituration with diethyl ether, the compound (39) as an orange solid (175 mg, 92%). IR νmax (cm−1): 2217 (νCN); 1H NMR (DMSO, 500 MHz) δ (ppm): 7.29 (2H, t, J10′-9′=J12′-13′=J10′-F=J12′-F=8.5 Hz, H10′ and H12′), 7.52 (1H, dm, J6′-7′=8.9 Hz, H6′), 7.55 (1H, dd, J5″-4″=7.9 Hz, J5″-6″=4.9 Hz, H5″), 7.59 (1H, d, J7′-6′=8.9 Hz, H7′), 7.78 (2H, dd, J9′-10′=J13′-12′=8.5 Hz et J9′-F=J13′-F=5.5 Hz, H9′ and H13′), 7.89 (1H, m, H4′), 7.91 (1H, s, H3), 8.23 (1H, s, H2′), 8.34 (1H, d, J4″-5″=7.9 Hz, H4″), 8.60 (1H, d, J6″-5″=4.9 Hz, H6″), 9.01 (1H, s, H2″), 11.86 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 108.4 (C2), 111.4 (C3′), 113.4 (C7′), 116.0 (2C, d, 2JC—F=21 Hz, C10′ and C12′), 118.1 (C2′), 118.6 (C1), 122.6 (C6′), 124.1 (C5″), 124.7 (C3a′), 128.4 (C4′), 129.4 (2C, d, 3JC—F=8 Hz, C9′ and C13′), 131.4 (C3″), 132.9 (C7a′), 133.8 (C3), 135.2 (C4″), 137.2 (C5′), 138.4 (C8′), 150.1 (C6″), 150.5 (C2″), 162.0 (1C, d, 1JC—F=244 Hz, C4″); ESI-MS: m/z 340.1 ([M+H]+); HRESI-MS: m/z 340.1241 (calcd for C22H15N3F, 340.1250).

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, 50/50 to 30/70)
  8. customto afford

Sources & evidence

ORD record
ord-952540614f25405c959c58135fb7001f
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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