1,4-Dioxane → HCID 69675631, compound

HRID 1616069Notes

Reaction equation

HRID 1616069 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]([NH:14]C(=O)OC(C)(C)C)[CH3:13])[C:6]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)=[C:5]2[C:28]1[O:32][N:31]=[C:30]([CH3:33])[N:29]=1.O1CCOCC1>C(Cl)Cl.Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]([NH2:14])[CH3:13])[C:6]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)=[C:5]2[C:28]1[O:32][N:31]=[C:30]([CH3:33])[N:29]=1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 69675865HCID 69675865, compound

Product 1

HCID 69675631HCID 69675631, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 1-(6-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate (0.246 g, 0.547 mmol) in DCM (1.095 mL) and hydrochloric acid, 4M solution in 1,4-dioxane (2.74 mL, 10.95 mmol) was stirred at rt. After 2.5 h, the mixture was partitioned between DCM (50 mL) and water (50 mL). The acidic aq mixture was washed with DCM (30 mL×2) to remove organic impurities. The aq layer was basified to ˜pH 13 with 10 N NaOH (1.5 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with water (100 mL×1), dried over MgSO4, filtered, and concentrated in vacuo to give 1-(6-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(pyridin-2-yl)-quinolin-2-yl)ethanamine as a light yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.59-8.64 (1H, m), 8.29 (1H, dd, J=9.3, 5.6 Hz), 7.83-7.92 (2H, m), 7.76 (1H, dd, J=10.0, 2.7 Hz), 7.50 (1H, d, J=7.8 Hz), 7.44 (1H, ddd, J=7.6, 4.9, 1.2 Hz), 4.03 (1H, q, J=6.7 Hz), 2.38 (3H, s), 2.03 (2H, br. s.), 1.24 (3H, d, J=6.5 Hz); LC-MS (ESI) m/z 350.1 [M+H]+. The light yellow syrup was carried on crude without purification for the next step.

Workup

  1. customthe mixture was partitioned between DCM (50 mL) and water (50 mL)
  2. washThe acidic aq mixture was washed with DCM (30 mL×2)
  3. customto remove organic impurities
  4. extractionextracted with DCM (50 mL×3)
  5. washThe combined organic layers were washed with water (100 mL×1)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cdd40697169e4b2b9cc7804318f3534f
Source dataset
uspto-grants-2014_07
Patent number
US08765768B2

Reaction notes

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