Methanol → 7-(3-Methoxy-pyridin-2-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine

HRID 1262419Notes

Reaction equation

HRID 1262419 reaction equation
[CH3:1][O:2][C:3]1[C:4]([Sn](CCCC)(CCCC)CCCC)=[N:5][CH:6]=[CH:7][CH:8]=1.Br[C:23]1[N:31]2[C:26]([CH:27]=[N:28][C:29]([S:32][CH3:33])=[N:30]2)=[CH:25][CH:24]=1.CO.C(Cl)Cl>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:1][O:2][C:3]1[C:4]([C:23]2[N:31]3[C:26]([CH:27]=[N:28][C:29]([S:32][CH3:33])=[N:30]3)=[CH:25][CH:24]=2)=[N:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 441182303-Methoxy-2-(tributylstannyl)pyridineHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 667127347-(3-Methoxy-pyridin-2-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazineYield 34.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-Methoxy-2-tributylstannanyl-pyridine (1.31 g, 3.29 mmol) was dissolved in N,N-Dimethylformamide (15 mL), 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.504 g, 2.06 mmol) and Tetrakis(triphenylphosphine)palladium(0) (161 mg, 0.139 mmol) were added, and the mixture was degassed under vacuum, then under an atmosphere of Nitrogen, was heated in a block at 80° C. for 8 h, then 110 C overnight. Bis(tri-tert-butylphosphine)palladium (45 mg, 0.088 mmol) was added and heating was continued at 110 C for 8 h. The mixture was cooled, conc. in vacuo and applied to a 25 g Isco cartridge (MeOH:DCM), dried and purified (80 g column, 0-70% EtOAc:Hex) to afford 7-(3-Methoxy-pyridin-2-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.192 g; Yield=34.1%). LCMS (HPLC):0.78 min, m/z=273 (M+H); 1H-NMR (DMSO-d6): 9.04 (s, 1H), 8.29 (d, 1H, J=4.4 Hz), 7.64 (d, 1H, J=8.4 Hz), 7.50 (dd, 1H, J=4.4, 8.4 Hz), 7.12 (d, 1H, J=4.6 Hz), 7.07 (d, 1H, J=4.6 Hz), 3.83 (s, 3H), 2.38 (s, 3H).

Workup

  1. customthe mixture was degassed under vacuum
  2. custom110 C overnight
  3. temperatureheating
  4. temperatureThe mixture was cooled, conc. in vacuo
  5. customdried
  6. custompurified (80 g column, 0-70% EtOAc:Hex)

Sources & evidence

ORD record
ord-7d881b1589cc42b68d26279d836d4116
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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