3-Fluoro-N-methoxy-N-methylbenzamide → (3-fluorophenyl)(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-6-quinolinyl)methanone

HRID 551534Notes

Reaction equation

HRID 551534 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[CH3:19])[CH:6]=[CH:5]2.C([Li])CCC.[F:25][C:26]1[CH:27]=[C:28]([CH:35]=[CH:36][CH:37]=1)[C:29](N(OC)C)=[O:30]>C1COCC1>[F:25][C:26]1[CH:27]=[C:28]([C:29]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([CH2:12][CH2:13][N:14]2[CH2:18][CH2:17][CH2:16][C@H:15]2[CH3:19])[CH:6]=[CH:5]3)=[O:30])[CH:35]=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 212657573-Fluoro-N-methoxy-N-methylbenzamideHCID 671046156-bromo-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}quinolineHCID 178418339Butyllithium

Product 1

HCID 25197092(3-fluorophenyl)(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-6-quinolinyl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The product from Example 42D (320 mg, 1.0 mmol) in THF (10 mL) was treated with 2.5M n-butyllithium (0.5 mL, 1.25 mmol) at −78° C. The solution was mixed for 15 min, and treated with a solution of 3-fluoro-N-methoxy-N-methylbenzamide (2.0 mmol) in THF (5.0 mL) at −78° C. The mixture was allowed to warm to room temperature overnight, quenched by 1 mL ethanol, concentrated, and diluted with ethyl acetate. The mixture was washed with 5% NaHCO3 (25 mL×3), 25% brine (25 mL), dried over Na2SO4, filtered, and the filtrate was concentrated to dryness. The residue was purified by column chromatography (heptane:acetone:CH2Cl2:TEA (60:40:5:1) to provide the title compound. The title compound was treated with HCl in IPA:ethyl acetate to give the dihydrochloride salt. mp 162-164° C. (dec.); MS (ESI) 363 (M+H)+; 1H NMR (DMSO-d6) δ 8.79 (1H, d), 8.53 (1H, d), 8.30 (1H, d), 8.21 (1H, dd), 7.82 (1H, d), 7.6 (4H, m), 3.9 (1H, br, m), 3.63 (2H, br, m), 3.50 (2H, br, m), 3.21 (1H, br, m), 2.2 (1H, m), 1.98 (2H, br, m), 1.7 (1H, br, m), 1.46 (1H, m), 1.30 (3H, d).

Workup

  1. additionThe solution was mixed for 15 min
  2. customquenched by 1 mL ethanol
  3. concentrationconcentrated
  4. additiondiluted with ethyl acetate
  5. washThe mixture was washed with 5% NaHCO3 (25 mL×3), 25% brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated to dryness
  9. customThe residue was purified by column chromatography (heptane:acetone:CH2Cl2:TEA (60:40:5:1)

Sources & evidence

ORD record
ord-685d18140a734beb94dc9516d948a375
Source dataset
uspto-grants-2011_05
Patent number
US07947711B2

Reaction notes

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