Cesium carbonate → 2-Acetamido-7-[(3-fluorophenethylamino)methyl]quinoline

HRID 1503147Notes

Reaction equation

HRID 1503147 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[F:7][C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[CH2:11][CH2:12][NH2:13].[C:17]([NH:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][C:25]([CH2:31]Br)=[CH:26][CH:27]=2)[N:22]=1)(=[O:19])[CH3:18]>CN(C=O)C>[C:17]([NH:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][C:25]([CH2:31][NH:13][CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[C:8]([F:7])[CH:9]=3)=[CH:26][CH:27]=2)[N:22]=1)(=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5339282-(3-Fluorophenyl)ethanamineHCID 11311996N-(7-(bromomethyl)quinolin-2-yl)acetamide

Product 1

HCID 1182521852-Acetamido-7-[(3-fluorophenethylamino)methyl]quinolineYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Anhydrous Cs2CO3 (0.295 g, 0.906 mmol) was diluted in anhydrous DMF (10 mL). 3-Fluorophenethylamine (22, 0.126 g, 0.906 mmol) was added, and the mixture was stirred at room temperature for 30 min before a solution of 21 (0.220 g, 0.788 mmol) in DMF (4 mL) was added slowly over 5 min. The cloudy yellow mixture was stirred at room temperature for 16 h and concentrated. The residue was diluted with EtOAc (50 mL) and washed with H2O (2×50 mL) and sat. aq. NaCl (50 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by flash column chromatography (SiO2) eluting with 10% MeOH in EtOAc to yield the product as a clear yellow oil (0.187 g, 70%). 1H-NMR (500 MHz; CDCl3): δ 8.95 (s, 1 H), 8.40 (br d, J=8.2 Hz, 1 H), 8.15 (d, J=8.9 Hz, 1 H), 7.74 (d, J=8.3 Hz, 1 H), 7.72 (s, 1 H), 7.41 (dd, J=8.3, 1.5 Hz, 1 H), 7.26-7.22 (m, 1 H), 6.98 (d, J=7.7 Hz, 1 H), 6.93-6.88 (m, 2 H), 4.00 (s, 2 H), 2.95 (t, J=7.0 Hz, 2 H), 2.85 (t, J=7.0 Hz, 2 H), 2.23 (s, 3 H); 13C NMR (126 MHz; CDCl3): δ 169.3 (1 C), (163.9+162.0, 1 C), 151.3 (1 C), 146.5 (1 C), (142.47+142.41, 1 C), 142.37 (1 C), 138.5 (1C), (129.95+129.88, 1 C), 127.8 (1 C), 125.76 (1 C), 125.71 (1 C), 125.4 (1 C), (124.42+124.40, 1 C), (115.63+115.46, 1 C), 114.0 (1 C), (113.23+113.06, 1 C), 53.7 (1 C), 50.1 (1 C), 36.1 (1 C), 24.9 (1 C); ESIMS m/z (rel. intensity) 338 (MH+, 80).

Workup

  1. additionwas added slowly over 5 min
  2. concentrationconcentrated
  3. additionThe residue was diluted with EtOAc (50 mL)
  4. washwashed with H2O (2×50 mL) and sat. aq. NaCl (50 mL)
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (SiO2)
  8. washeluting with 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-5da892e2977d47999b8f699c1810e00d
Source dataset
uspto-grants-2015_12
Patent number
US09212144B2

Reaction notes

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