Benzenamine, 4-(4-morpholinyl)- → HCID 10299410, compound

HRID 1181994Notes

Reaction equation

HRID 1181994 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([N:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)[CH:12]=1)[N:9]=[C:8]([C:20]([OH:22])=O)[CH:7]=[C:6]2[O:23][CH3:24].[O:25]1[CH2:30][CH2:29][N:28]([C:31]2[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=2)[CH2:27][CH2:26]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[N:28]1([C:31]2[CH:32]=[CH:33][C:34]([NH:35][C:20]([C:8]3[CH:7]=[C:6]([O:23][CH3:24])[C:5]4[C:10](=[C:11]([N:13]5[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]5)[CH:12]=[C:3]([F:2])[CH:4]=4)[N:9]=3)=[O:22])=[CH:36][CH:37]=2)[CH2:27][CH2:26][O:25][CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 757711-HydroxybenzotriazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 69269711HCID 69269711, compound

Product 1

HCID 10299410HCID 10299410, compoundYield 93.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 250 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer is added 2.01 g (6.3 mmol, 1.0 equiv.) of 6-Fluoro-4-methoxy-8-(4-methyl-piperazin-1-yl)-quinoline-2-carboxylic acid hydrochloride salt. This material is dissolved in 20 mL of DMF and then 1.35 g (7.56 mmol, 1.2 equiv.) of 4-morpholinoaniline is added. To the stirred solution is quickly added simultaneously added 4.05 g (12.6 mmol, 2.0 equiv.) of TBTU (2-(1H-benzotriazole-1-yl)-1,1,3,3tetramethyluroniumtetrafluoroborate) and 1.7 g (12.6 mmol, 2.0 equiv.) of HOBT (1-hydroxybenzotriaole hydrate). At this point 3.25 g, 4.11 mL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes. The reaction is allowed to stir at room temperature for 18 hrs, then is concentrated on a rotary evaporator under high vacuum in order to remove the DMF. The residue is triturated with methanol and the crude solids are recovered by filtration. The material is then dissolved in methylene chloride and extracted with 10% sodium bicarbonate solution. The organic layer is dried and then concentrated. These residues are then purified by flash chromatography using a gradient of 5-10% methanol in methylene chloride as eluent. The material which is obtained from chromatography, is then crystallized from methanol to give the pure product as 2.83 g (93%) of a yellow solid.

Workup

  1. customInto a 250 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer
  2. additionAt this point 3.25 g, 4.11 mL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes
  3. concentrationis concentrated on a rotary evaporator under high vacuum in order
  4. customto remove the DMF
  5. customThe residue is triturated with methanol
  6. filtrationthe crude solids are recovered by filtration
  7. dissolutionThe material is then dissolved in methylene chloride
  8. extractionextracted with 10% sodium bicarbonate solution
  9. customThe organic layer is dried
  10. concentrationconcentrated
  11. customThese residues are then purified by flash chromatography
  12. customThe material which is obtained from chromatography
  13. customis then crystallized from methanol

Sources & evidence

ORD record
ord-35d0c50899f64a4987400d11b9b5b469
Source dataset
uspto-grants-2007_10
Patent number
US07285662B2

Reaction notes

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