Diethyl Ether → HCID 49853608, compound

HRID 1503135Notes

Reaction equation

HRID 1503135 reaction equation
[C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6](C(OC(C)(C)C)=O)[CH:5]=1)#[N:2].[H-].[Na+].[Cl:24][C:25]1[N:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.C(OCC)C>C1COCC1.C(Cl)Cl.CCO>[Cl:24][C:25]1[N:30]=[CH:29][C:28](/[CH:31]=[C:3](/[C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=3)[NH:6][CH:5]=2)\[C:1]#[N:2])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 27640536-Chloropyridine-3-carbaldehydeHCID 11616206tert-Butyl 3-(cyanomethyl)-5-methoxy-1H-indole-1-carboxylate

Product 1

HCID 49853608HCID 49853608, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

To a solution of tert-butyl 3-(cyanomethyl)-5-methoxy-1H-indol-1-carboxylate (4.9 g, 17 mmol, 1.0 eq.) in anhydrous THF (400 mL) was added, under an argon atmosphere, NaH (930 mg, 80%, 31 mmol, 1.8 eq.). The mixture was stirred at room temperature for 10 minutes, and then cooled to 0° C. before the addition of 6-chloro-pyridine-3-carbaldehyde (3 g, 21 mmol, 1.2 eq.). The reaction apparatus was protected from light and the mixture was stirred 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 dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1) to afford, after trituration with diethyl ether, the compound (49) as a yellow powder (3.8 g, 72%). TLC: Rf=0.40 (CH2Cl2/EtOH, 96/4); mp: 184° C.; IR νmax (cm−1): 2208 (νCN); 1H NMR (DMSO, 300 MHz) δ (ppm): 3.83 (3H, s, 5′-methoxy), 6.90 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.40 (1H, d, J7′-6′=8.9 Hz, H7′), 7.49 (1H, d, J4′-6′=2.4 Hz, H4′), 7.67 (1H, d, J5″-4″=8.5 Hz, H5″), 7.73 (1H, s, H3), 7.79 (1H, s, H2′), 8.37 (1H, dd, J4″-5″=8.5 Hz, J4″-2″=2.4 Hz, H4″), 8.81 (1H, d, J2″-4″=2.4 Hz, H2″), 11.70 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 55.6 (5′-methoxy), 102.0 (C4′), 108.2 (C2), 110.1 (C3′), 112.4 (C6′), 113.2 (C7′), 117.8 (C1), 123.9 (C3a′), 124.2 (C5″), 128.0 (C2′), 130.3 (C3), 130.4 (C3″), 132.3 (C7a′), 137.9 (C4″), 149.8 (C6″), 150.2 (C2″), 154.6 (C5′); ESI-MS: 310.1 ([M+H]+), 334.1 ([M+Na]+); HRESI-MS: m/z 310.0733 (calcd for C17H13N3O35Cl+, 310.0747).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1)
  7. customto afford

Sources & evidence

ORD record
ord-f50a93b5518e4f73824b5b22036fead7
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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