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

HRID 1473331노트

반응식

HRID 1473331 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
110 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-fb22f793bb484ba5a66f5a8b0884f53b
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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