Morpholine → N-{5-(2-methoxyethoxy)-2-[(4R)-4-(morpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylpyridine-2-sulfonamide

HRID 1994955Notes

Reaction equation

HRID 1994955 reaction equation
CS(O[CH2:6][C@@H:7]1[CH2:11][S:10][C:9]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[CH:16][C:15]=3[N:26]([CH3:36])[S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)(=[O:29])=[O:28])=[N:8]1)(=O)=O.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:25][O:24][CH2:23][CH2:22][O:21][C:17]1[CH:18]=[C:19]2[C:14](=[C:15]([N:26]([CH3:36])[S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)(=[O:29])=[O:28])[CH:16]=1)[NH:13][C:12]([C:9]1[S:10][CH2:11][C@@H:7]([CH2:6][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[N:8]=1)=[CH:20]2

Participants

5

Reactant 3

HCID 8083Morpholine2×HCID 11430Potassium Carbonate2×HCID 59135898((4R)-2-{5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-4-yl)methyl methanesulfonate

Product 1

HCID 59135750N-{5-(2-methoxyethoxy)-2-[(4R)-4-(morpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylpyridine-2-sulfonamideYield 2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of ((4R)-2-{5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-4-yl)methyl methanesulfonate (0.1 g), morpholine (0.032 mL) and potassium carbonate (0.050 g) in N,N-dimethylformamide (5 mL) was stirred at room temperature for 18 hr, and the mixture was stirred at 50° C. for 6 hr. The same amount of morpholine (0.032 mL) and potassium carbonate (0.050 g) were added, and the mixture was stirred at 80° C. for 18 hr. The reaction mixture was concentrated, and the residue was extracted with ethyl acetate. The ethyl acetate layer was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate-methanol (4:1:0-0:10:1, volume ratio) to give the title compound (0.002 g, yield 2%) as a colorless amorphous solid.

Workup

  1. stirringthe mixture was stirred at 80° C. for 18 hr
  2. concentrationThe reaction mixture was concentrated
  3. extractionthe residue was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. washeluted with hexane-ethyl acetate-methanol (4:1:0-0:10:1, volume ratio)

Sources & evidence

ORD record
ord-2fd0ab50ca6549c692f2639b77df5d69
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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