Isopropyl iodide → HCID 49854630, compound

HRID 2368841Notes

Reaction equation

HRID 2368841 reaction equation
[C:1]([C:3]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([OH:20])[CH:18]=2)[N:13](C(OC(C)(C)C)=O)[CH:12]=1)=[CH:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)#[N:2].[CH:28](I)([CH3:30])[CH3:29].C(=O)([O-])[O-].[K+].[K+].C[O-].[Na+]>CS(C)=O.CCCCCCC.C(OCC)C>[CH:28]([O:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2/[C:3](=[CH:4]/[C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)/[C:1]#[N:2])([CH3:30])[CH3:29]

Participants

8

Reactant 4

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 10942334Sodium MethoxideHCID 67514100HCID 67514100, compound

Product 1

HCID 49854630HCID 49854630, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 8900HeptaneSolvent2×

Procedure

To a solution of tert-butyl 3-(1-cyano-2-(pyridin-3-yl)vinyl)-5-hydroxy-1H-indole-1-carboxylate (see example 22) (110 mg, 0.30 mmol, 1.0 eq.) and isopropyl iodide (40 μL, 0.40 mmol, 1.3 eq.) in DMSO (8 mL) was added potassium carbonate (100 mg, 0.73 mmol, 2.4 eq.). The reaction apparatus was protected from light and the mixture was stirred at room temperature for 24 hours before sodium methanolate (41 mg, 0.75 mmol, 2.5 eq.) was added. The reaction was pursued at room temperature for 1 hour, and then quenched with a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 60:40 to 40:60) to afford, after trituration with diethyl ether, the compound (23) as a yellow powder (50 mg, 55%). TLC: Rf=0.25 (heptane 40/EtOAc 60); mp: 211° C.; IR νmax (cm-1): 2218 (νCN); 1H NMR (DMSO, 300 MHz): δ (ppm): 1.29 (6H, d, J9′-8′=J9′-8′=6.1 Hz, 3H9′ and 3H10′), 4.65 (1H, h, J8′-9′=J8′-9′=6.1 Hz, H8′), 6.90 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.39 (1H, d, J7′-6′=8.9 Hz, H7′), 7.51 (1H, d, J4′-6′=2.1 Hz, H4′), 7.54 (1H, dd, J5″-4″=7.9 Hz, J5″-6″=4.9 Hz, H5″), 7.73 (1H, s, H3), 7.79 (1H, s, H2′), 8.32 (1H, d, J4″-5″=7.9 Hz, H4″), 8.59 (1H, dd, J6″-5″=4.9 Hz, J6″-4″=1.2 Hz, H6″), 8.98 (1H, d, J2″-4″=1.6 Hz, H2″), 11.64 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 22.5 (C9′ and C10′), 70.7 (C8′), 105.9 (C4′), 108.7 (C2), 110.6 (C3′), 113.6 (C6′), 114.6 (C7′), 118.6 (C1), 124.1 (C5″), 124.6 (C3a′), 128.1 (C2′), 131.4 (C3″), 132.7 (C3), 132.9 (C7a′), 135.1 (C4″), 150.0 (C6″), 150.4 (C2″), 152.9 (C5′); ESI-MS: m/z 304.1 ([M+H]+), 326.1 ([M+Na]+); HRESI-MS: m/z 304.1448 (calcd for C19H18N3O, 304.1450).

Workup

  1. additionwas added
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed under reduced pressure
  7. customthe residue purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 60:40 to 40:60)
  8. customto afford

Sources & evidence

ORD record
ord-ba23df7d2aae4a1e8b45488be60307aa
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

Loading…