5-Methyl-2-(tri-n-butylstannyl)pyridine → 1-methyl-2-(1-(2-methyl-6-(5-methylpyridin-2-yl)pyrimidin-4-yl)azetidin-3-yl)-1H-benzo[d]imidazole

HRID 2202823Notes

Reaction equation

HRID 2202823 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][CH:7]=1.Cl[C:22]1[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29]2[CH2:32][CH:31]([C:33]3[N:37]([CH3:38])[C:36]4[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=4[N:34]=3)[CH2:30]2)[CH:23]=1>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.CN(C=O)C>[CH3:38][N:37]1[C:36]2[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=2[N:34]=[C:33]1[CH:31]1[CH2:32][N:29]([C:24]2[CH:23]=[C:22]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[N:27]=[C:26]([CH3:28])[N:25]=2)[CH2:30]1

Participants

5

Reactant 2

HCID 111327115-Methyl-2-(tri-n-butylstannyl)pyridineHCID 894935592-(1-(6-chloro-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

Product 1

HCID 715500981-methyl-2-(1-(2-methyl-6-(5-methylpyridin-2-yl)pyrimidin-4-yl)azetidin-3-yl)-1H-benzo[d]imidazole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a microwave vial was added 5-methyl-2-(tributylstannyl)pyridine (97 mg, 2.6 mmol), Intermediate 3 (40 mg, 0.13 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol), and DMF (1 mL). The vial was sealed and heated in a heating block at 110° C. for 16 h. The reaction was cooled to room temperature, passed through a syringe filter, and purified by reverse-phase chromatography (5-55% acetonitrile/water/0.1% TFA). The product fractions were poured into aqueous NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to give Example 94 as a white solid. 1H NMR: (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.75 (d, J=7.3 Hz, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.29 (m, 3H), 7.15 (s, 1H), 4.66 (m, 4H), 4.29 (m, 1H), 3.74 (s, 3H), 2.60 (s, 3H), 2.40 (s, 3H) ppm. MS: m/z=371.5 (M+H).

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. custompassed through a syringe
  4. filtrationfilter
  5. custompurified by reverse-phase chromatography (5-55% acetonitrile/water/0.1% TFA)
  6. additionThe product fractions were poured into aqueous NaHCO3
  7. extractionextracted with EtOAc
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-cbb4a492f3654fba8a943fae9408d3c3
Source dataset
uspto-grants-2016_06
Patent number
US09365562B2

Reaction notes

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