Triethylamine → N-(2-chloro-4-{[(4-hydroxytetrahydro-2H thiopyran-4-yl)methyl]amino}quinolin-3-yl)butanamide

HRID 44772Notes

Reaction equation

HRID 44772 reaction equation
[C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[NH2:7][C:8]1[C:9]([Cl:27])=[N:10][C:11]2[C:16]([C:17]=1[NH:18][CH2:19][C:20]1([OH:26])[CH2:25][CH2:24][S:23][CH2:22][CH2:21]1)=[CH:15][CH:14]=[CH:13][CH:12]=2.C(N(CC)CC)C>ClCCl.C(=O)(O)[O-].[Na+]>[Cl:27][C:9]1[C:8]([NH:7][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[C:17]([NH:18][CH2:19][C:20]2([OH:26])[CH2:25][CH2:24][S:23][CH2:22][CH2:21]2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 8855Butyryl chloride2×HCID 872048714-{[(3-Amino-2-chloroquinolin-4-yl)amino]methyl}tetrahydro-2h-thiopyran-4-ol

Product 1

HCID 87204895N-(2-chloro-4-{[(4-hydroxytetrahydro-2H thiopyran-4-yl)methyl]amino}quinolin-3-yl)butanamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Under a nitrogen atmosphere butyryl chloride (322 μL, 3.11 mmol) was added dropwise was added to a suspension of 4-{[(3-amino-2-chloroquinolin-4-yl)amino]methyl}tetrahydro-2H-thiopyran-4-ol (0.92 g, 2.83 mmol) in dichloromethane (28 mL). After 2 hours triethylamine (0.79 mL, 5.66 mol) was added and the reaction mixture was stirred for 2 hours. More butyryl chloride (0.2 mL) and triethylamine (0.30 mL) were added. The reaction mixture was stirred for an additional hour and then diluted with saturated aqueous sodium bicarbonate (50 mL) and extracted with dichloromethane (3×60 mL). The combined organics were washed with saturated aqueous sodium bicarbonate (40 mL) and brine (30 mL), dried over sodium sulfate, filtered, and then concentrated under reduced pressure to provide N-(2-chloro-4-{[(4-hydroxytetrahydro-2H thiopyran-4-yl)methyl]amino}quinolin-3-yl)butanamide as an off-white solid.

Workup

  1. stirringThe reaction mixture was stirred for an additional hour
  2. extractionextracted with dichloromethane (3×60 mL)
  3. washThe combined organics were washed with saturated aqueous sodium bicarbonate (40 mL) and brine (30 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-525eebb8562b4025b9c1e18ed3a2615e
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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