Potassium Carbonate → 7-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

HRID 1262410노트

반응식

HRID 1262410 반응식
[CH3:1][S:2][C:3]1[N:8]=[CH:7][C:6]2=[CH:9][CH:10]=[C:11]([C:12]3[CH:13]=[C:14]([NH2:18])[CH:15]=[CH:16][CH:17]=3)[N:5]2[N:4]=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:35][CH2:36][CH2:37][S:38](Cl)(=[O:40])=[O:39]>CN(C)C=O.CCOC(C)=O.O>[O:39]=[S:38]1(=[O:40])[CH2:37][CH2:36][CH2:35][N:18]1[C:14]1[CH:13]=[C:12]([C:11]2[N:5]3[C:6]([CH:7]=[N:8][C:3]([S:2][CH3:1])=[N:4]3)=[CH:9][CH:10]=2)[CH:17]=[CH:16][CH:15]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 154103-Chloropropanesulphonyl chloride2회HCID 81531Diisopropylethylamine2회HCID 667126823-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine

생성물 1

HCID 667117407-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine수율 46.5%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine (0.795 g, 3.10 mmol) was dissolved in N,N-Dimethylformamide (12.0 mL) and N,N-Diisopropylethylamine (1.50 mL, 8.61 mmol). Potassium carbonate (1.28 g, 9.30 mmol) was added, followed by 3-Chloropropane-1-sulfonyl chloride (0.450 mL, 3.70 mmol) and stirred overnight. After 24 h, a second aliquot of N,N-Diisopropylethylamine (2.00 mL, 11.5 mmol) and 3-Chloropropane-1-sulfonyl chloride (0.50 mL, 4.1 mmol) was added and stirred additionally. When conversion had reached ca. 90%, the mixture was treated with water (40 mL) and EtOAc (40 mL). The layers were separated, the aq. extr. with EtOAc (3×20 mL) and the comb. org. diluted with hexane (20 mL) and washed with water (30 ml) and brine (30 mL). After drying over sodium sulfate, the mixture was filtered and conc. in vacuo and applied to a 25 g ISCO loading cartridge. Purification on ISCO (40 g column, 10-70% EtOAc:Hex) afforded 7-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine (0.52 g; Yield=46%) as a yellow solid. 1H-NMR (CDCl3): 8.74 (s, 1H), 8.06 (s, 1H), 7.86 (d, 1H, J=7.9 Hz), 7.47 (m, 1H), 7.28 (m, 1H), 7.27 (s, 1H), 7.12 (d, 1H, J=4.8 Hz), 6.89 (d, 1H, J=4.8 Hz), 3.86 (t, 2H, J=6.5 Hz), 3.42 (t, 2H, J=7.4 Hz), 2.62 (s, 3H), 2.58 (m, 2H).

후처리

  1. waitAfter 24 h
  2. stirringstirred additionally
  3. customThe layers were separated
  4. additiondiluted with hexane (20 mL)
  5. washwashed with water (30 ml) and brine (30 mL)
  6. dry with materialAfter drying over sodium sulfate
  7. filtrationthe mixture was filtered and conc. in vacuo
  8. customPurification on ISCO (40 g column, 10-70% EtOAc:Hex)

출처 및 근거

ORD 기록
ord-efe2dbe425ee4d9d9349e5f0f34b9030
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08471005B2

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