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

HRID 1262410Notes

Reaction equation

HRID 1262410 reaction equation
[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

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 154103-Chloropropanesulphonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 667126823-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-efe2dbe425ee4d9d9349e5f0f34b9030
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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