Diethyl Ether → HCID 49853607, 화합물

HRID 1503134노트

반응식

HRID 1503134 반응식
[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[C:30]([CH:31]=O)=[CH:29][CH:28]=[CH:27][N:26]=1.C(OCC)C>C1COCC1>[F:24][C:25]1[C:30](/[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:29][CH:28]=[CH:27][N:26]=1

참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 114349442-Fluoropyridine-3-carbaldehydeHCID 11616206tert-Butyl 3-(cyanomethyl)-5-methoxy-1H-indole-1-carboxylate

생성물 1

HCID 49853607HCID 49853607, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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 2-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 24 hours, at room temperature for 24 hours too and then, quenched with a saturated aqueous ammonium chloride solution. The mixture was stirred again at room temperature for 24 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 (48) as a yellow powder (220 mg, 30%). IR νmax (cm-1): 2219 (νCN), 3228 (νN—H); 1H NMR (DMSO, 300 MHz): δ (ppm): 3.81 (3H, s, 5′-methoxy), 6.91 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.42 (1H, d, J7′-6′=8.9 Hz, H7′), 7.43 (1H, d, J4′-6′=2.4 Hz, H4′), 7.53 (1H, m, H5″), 7.64 (1H, s, H3), 7.84 (1H, s, H2′), 8.29 (1H, d, J6″-5″=4.5 Hz, H6″), 8.49 (1H, m, H4″), 11.73 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.5 (5′-methoxy), 101.5 (C4′), 109.8 (C2), 110.0 (C3′), 112.5 (C6′), 113.3 (C7′), 117.3 (C1), 118.0 (1C, d, 2JC—F=28 Hz, C3″), 122.3 (1C, d, 4JC—F=4 Hz, C5″), 123.9 (C3a′), 125.8 (C3), 128.1 (C2′), 132.2 (C7a′), 139.4 (1C, d, 3JC—F=3 Hz, C4″), 147.5 (1C, d, 3JC—F=15 Hz, C6″), 154.7 (C5′), 159.7 (1C, d, 1JC—F=270 Hz, C2″); ESI: 294.1 ([M+H]+), 316.1 ([M+Na]+), 348.1 ([M+Na+ MeOH]+); HRESI-MS: m/z 316.0861 (calcd for C17H12N3OFNa+, 316.0862).

후처리

  1. stirringthe mixture was stirred at 0° C. for 24 hours, at room temperature for 24 hours too
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. stirringThe mixture was stirred again at room temperature for 24 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

출처 및 근거

ORD 기록
ord-6e7a34d3b5324d59964c31bba8f14ed7
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212138B2

반응 노트

불러오는 중…