Morpholine → 1-morpholino-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473331Notes

Reaction equation

HRID 1473331 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CN(C=O)C.O>[O:30]1[CH2:31][CH2:32][N:27]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]4[S:17][CH:18]=[CH:19][N:20]=4)(=[O:14])=[O:13])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 866873831-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866873841-morpholino-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

1-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.200 g, 0.614 mmol) and potassium carbonate (0.424 g, 3.07 mmol) were dissolved in DMF (4.09 ml). Morpholine (0.535 ml, 6.14 mmol) was added and the reaction was stirred overnight at 110° C. The reaction was diluted with water and extracted twice with ethyl acetate. The aqueous layer was acidified to a pH of about 1 with concentrated HCl solution and extracted twice with ethyl acetate. The aqueous layer was passed through an SCX ion exchange column (pre-wetted with methanol) (Biotage AB, Uppsala, SE), then the column was washed several times with methanol. The product was liberated with ammonia solution in methanol. The process was repeated with the aqueous filtrate and a new SCX column. The product-containing filtrates were combined and concentrated to afford crude product as an orange solid. The material was purified by silica gel chromatography (40 g column, gradient elution 0-10% MeOH:DCM) to afford 1-morpholino-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=12.86 (br. s., 1H), 8.38 (d, J=1.9 Hz, 1H), 8.28-8.19 (m, 2H), 7.86 (dd, J=1.9, 8.9 Hz, 1H), 7.62 (d, J=5.5 Hz, 1H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.88-3.80 (m, 4H), 3.35-3.26 (m, 4H). m/z (ESI) 377.2 (M+H)+.

Workup

  1. extractionextracted twice with ethyl acetate
  2. extractionextracted twice with ethyl acetate
  3. washthe column was washed several times with methanol
  4. concentrationconcentrated
  5. customto afford crude product as an orange solid
  6. customThe material was purified by silica gel chromatography (40 g column, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-fb22f793bb484ba5a66f5a8b0884f53b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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