Tetrahydrofuran → HCID 54453418, compound

HRID 1432916Notes

Reaction equation

HRID 1432916 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[C:25]([Cl:30])[CH:24]=[CH:23]2.C1COCC1.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:19][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25]([Cl:30])[CH:24]=[CH:23]3)[C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 112768896-(Bromomethyl)-2-chloroquinoline

Product 1

HCID 54453418HCID 54453418, compoundYield 85.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-oxopiperazine-1-carboxylic acid benzyl ester (4.65 g, 19.8 mmol) and 6-bromomethyl-2-chloroquinoline (5.40 g, 21.0 mmol) in 80 mL of a 3:1 mixture of THF:DMF at 0° C. is added sodium hydride (0.81 g, 20.2 mmol, 60% mineral oil dispersion). The resulting mixture is stirred for 1 hour at 0° C. then at room temperature for 18 hours. The reaction mixture is quenched with saturated NH4Cl solution, then diluted with EtOAc. The organic layer is washed sequentially with 1N HCl, water, saturated NaHCO3 and saturated NaCl, then dried over MgSO4, filtered and concentrated. The crude product is triturated in Et2O/hexanes/EtOAc and filtered to afford the title compound (6.96 g, 17.0 mmol) as a white solid. 1H NMR (CDCl3, 300 MHz) δ8.08 (d, 1H), 8.00 (d, 1H), 7.69 (s, 1H), 7,63 (dd, 1H), 7.41 (d, 1H), 7.35 (s, 5H), 5.15 (s, 2H), 4.78 (s, 2H), 4.28 (s, 2H), 3.70 (m, 2H), 3.32 (bs, 2H).

Workup

  1. waitat room temperature for 18 hours
  2. customThe reaction mixture is quenched with saturated NH4Cl solution
  3. additiondiluted with EtOAc
  4. washThe organic layer is washed sequentially with 1N HCl, water, saturated NaHCO3 and saturated NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is triturated in Et2O/hexanes/EtOAc
  9. filtrationfiltered

Sources & evidence

ORD record
ord-56c7ce6f8dbd43e8862b13517c5a2062
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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