Diethyl Ether → HCID 49854743, compound

HRID 1503124Notes

Reaction equation

HRID 1503124 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+].[F:24][C:25]1[N:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.C(OCC)C>C1COCC1>[F: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

6

Reactant 4

HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 11616206tert-Butyl 3-(cyanomethyl)-5-methoxy-1H-indole-1-carboxylateHCID 164142462-Fluoro-5-formylpyridine

Product 1

HCID 49854743HCID 49854743, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 3-(cyanomethyl)-5-methoxy-1H-indol-1-carboxylate (719 mg, 2.51 mmol, 1.0 eq.) in anhydrous THF (30 mL) was added, under an argon atmosphere, NaH (106 mg, 80%, 3.52 mmol, 1.4 eq.). The mixture was stirred at room temperature for 2 hours, and then cooled to 0° C. before the addition of 6-fluoro-pyridine-3-carbaldehyde (440 mg, 3.52 mmol, 1.4 eq.) in anhydrous THF (6 mL). The reaction apparatus was protected from light and the mixture was stirred at 0° C. for 4 hours, and then quenched with a saturated aqueous ammonium chloride solution. The mixture was stirred again at room temperature for 4 hours and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2) to afford, after trituration with diethyl ether, the compound (28) as a yellow powder (45 mg, 6%). IR νmax (cm-1): 2215 (νCN); 1H NMR (DMSO, 300 MHz): δ (ppm): 3.84 (3H, s, 5′-methoxy), 6.91 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.36 (1H, dd, J5″-4″=8.5 Hz, J5″-F=2.1 Hz, H5″), 7.41 (1H, d, J7′-6′=8.9 Hz, H7′), 7.49 (1H, d, J4′-6′=2.4 Hz, H4′), 7.76 (1H, s, H3), 7.78 (1H, s, H2′), 8.52 (1H, td, J5″-4″=J5″-F=10.1 Hz, J4″-2″=1.8 Hz, H4″), 8.67 (1H, d, J2″-4″=1.8 Hz, H2″), 11.66 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.6 (5′-methoxy), 102.0 (C4′), 108.2 (C2), 109.7 (1C, d, 2JC—F=37 Hz, C5″), 110.0 (C3′), 112.4 (C6′), 113.2 (C7′), 118.0 (C1), 124.0 (C3a′), 127.7 (C2′), 129.5 (1C, d, 4JC—F=4 Hz, C3″), 130.7 (C3), 132.3 (C7a′), 140.7 (1C, d, 3JC—F=8 Hz, C4″), 148.2 (1C, d, 3JC—F=15 Hz, C2″), 154.6 (C5′), 162.6 (1C, d, 1JC—F=237 Hz, C6″); ESI: 294.1 ([M+H]+), 316.1 ([M+Na]+), 348.1 ([M+Na+ MeOH]+); HRESI-MS: m/z 294.1052 (calcd for C17H13N3OF, 294.1043).

Workup

  1. stirringthe mixture was stirred at 0° C. for 4 hours
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. stirringThe mixture was stirred again at room temperature for 4 hours
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98:2)
  9. customto afford

Sources & evidence

ORD record
ord-eebb08762ab846f19611a57787af126c
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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