2-(Tributylstannyl)pyridine → HCID 68110067, compound

HRID 525080Notes

Reaction equation

HRID 525080 reaction equation
Br[C:2]1[C:10]2[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[CH2:21][CH3:22].C([Sn](CCCC)(CCCC)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)CCC>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:21]([C:3]1[S:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)[C:10]=2[C:2]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[CH3:22]

Participants

6

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 68110300HCID 68110300, compound

Product 1

HCID 68110067HCID 68110067, compoundYield 12.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 25 ml sealed tube containing a solution of 4-N-[5-bromo-6-ethylthieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (100 mg, 0.26 mmol, 1.00 equiv) in dioxane (5 mL) was added 2-(tributylstannyl)pyridine (96 mg, 0.26 mmol, 1.00 equiv) and Pd(dppf)Cl2 (30 mg, 0.04 mmol, 0.16 equiv) at room temperature under nitrogen. The sealed tube was heated with stirring overnight at 100° C. The reaction mixture was cooled to room temperature and diluted with 20 mL of H2O, extracted with 3×50 mL of ethyl acetate, washed with brine, dried over sodium sulfate and concentrated under vacuum. The crude product (80 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 49.0% in 27 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the corresponding 4-N-[6-ethyl-5-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (12 mg) as a light yellow oil. MS (ES, m/z): 382 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.75-8.41 (d, 1H), 7.90 (s, 1H), 7.89-7.84 (m, 1H), 7.46-7.38 (m, 2H), 6.73-6.71 (d, 1H), 3.95-3.89 (m, 1H), 2.89-2.81 (dd, 2, H), 2.29 (s, 6H), 2.25-2.04 (m, 3H), 1.90-1.86 (m, 2 H), 1.47-1.38 (m, 2H), 1.32-1.27 (m, 3H), 1.05-1.92 (m, 2H).

Workup

  1. customInto a 25 ml sealed tube
  2. temperatureThe sealed tube was heated
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with 3×50 mL of ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product (80 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  9. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 49.0% in 27 min)
  10. customThe product-containing fractions were collected
  11. custompartially evaporated
  12. customto remove water and CH3CN under reduced pressure
  13. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-d1b1249ae67a474baea6f57a8d45ad3e
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

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