Methanol → HCID 178521238, compound

HRID 2289999Notes

Reaction equation

HRID 2289999 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][C:9]([O:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[N:21]=[CH:20][C:19]([C:26]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)=[O:27])=[C:18]2[OH:37])=[O:10].CCN(CC)CC.CO>CN(C=O)C.C(Cl)Cl>[O:4]1[CH2:5][CH2:6][N:1]([CH2:8][C:9]([O:11][CH2:12][CH2:13][CH2:14][C:15]2[CH:16]=[C:17]3[C:22](=[C:23]([F:25])[CH:24]=2)[N:21]=[CH:20][C:19]([C:26]([NH:28][CH2:29][C:30]2[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=2)=[O:27])=[C:18]3[OH:37])=[O:10])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 887Methanol3×HCID 8083MorpholineHCID 8471TriethylamineHCID 178520141HCID 178520141, compound

Product 1

HCID 178521238HCID 178521238, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×

Procedure

Morpholine (0.03 mL) is added to a solution of 3-(3-{[(4-chlorobenzyl)amino]-carbonyl}-8-fluoro-4-hydroxy-6-quinolinyl)propyl 2-bromoacetate from Example No. 145 (0.10 g) and Et3N (0.040 mL) in 5 mL DMF. The reaction is stirred at room temperature after which time reaction is complete. The reaction is partitioned between CH2Cl2 (50 mL) and H2O (25 mL). The organic layer is washed twice with H2O, and once with brine. The aqueous layers are combined and back-extracted with CH2Cl2. The organics are combined, dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow liquid. The liquid is re-dissolved in CH2Cl2 and adsorbed onto silica. Chromatography on a Biotage Flash 40S column (eluent 1% MeOH:CH2Cl2 (1 L), followed by 2% MeOH:CH2Cl2 (2 L) and 5% MeOH:CH2Cl2 (1 L)) affords the desired product as a white solid (0.070 g, 68%).

Workup

  1. customafter which time reaction
  2. customThe reaction is partitioned between CH2Cl2 (50 mL) and H2O (25 mL)
  3. washThe organic layer is washed twice with H2O
  4. extractionback-extracted with CH2Cl2
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow liquid

Sources & evidence

ORD record
ord-5a4e4516dec4493793a09591c117618e
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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