1-Methyl-2-(tributylstannyl)-1H-imidazole → HCID 58949491, compound

HRID 1676409Notes

Reaction equation

HRID 1676409 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]([C:22]2[C:23](=[O:35])[N:24]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[N:25]=[CH:26][CH:27]=2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH3:36][N:37]1[CH:41]=[CH:40][N:39]=[C:38]1[Sn](CCCC)(CCCC)CCCC>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.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]([C:22]2[C:23](=[O:35])[N:24]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[N:25]=[CH:26][CH:27]=2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:38]3[N:37]([CH3:36])[CH:41]=[CH:40][N:39]=3)[S:17][C:10]=12

Participants

5

Reactant 2

HCID 27632521-Methyl-2-(tributylstannyl)-1H-imidazoleHCID 67348506N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Product 1

HCID 58949491HCID 58949491, compoundYield 75.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask was charged with N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (230 mg, 0.382 mmol), 1-methyl-2-(tributylstannyl)-1H-imidazole (850.3 mg, 2.29 mmol), tetrakis(triphenylphosphine)palladium (88.25 mg, 0.0764 mmol) and toluene (25 mL). The reaction mixture was stirred at 100° C. until LC-MS showed that the starting material had been consumed (4 hours). Then the reaction was cooled to room temperature and partitioned between EtOAc (100 mL) and H2O (100 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×100 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (159.8 mg, 75.2%). LRMS (APCI pos): >99% purity, 254 nm, m/e 557 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.82 (s, 1H), 8.50 (m, 1H), 8.41 (m, 1H), 8.22 (m, 1H), 7.98 (m, 1H), 7.46-7.42 (m, 4H), 7.40 (m, 2H), 7.24 (m, 2H), 6.98 (d, 1H), 6.54 (m, 1H), 3.84 (s, 3H).

Workup

  1. customhad been consumed (4 hours)
  2. temperatureThen the reaction was cooled to room temperature
  3. custompartitioned between EtOAc (100 mL) and H2O (100 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was re-extracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a crude product
  10. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1

Sources & evidence

ORD record
ord-93f47cf3e91244d6902676495af7bddf
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…