Lithium Hexamethyldisilazide → HCID 67347606, compound

HRID 1676328Notes

Reaction equation

HRID 1676328 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=4)[S:17][C:10]=23)=[CH:4][CH:3]=1.C[Si]([N-:32][Si](C)(C)C)(C)C.[Li+]>>[NH2:32][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=4)[S:17][C:10]=23)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 589494324-(7-(6-chloropyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide

Product 1

HCID 67347606HCID 67347606, compoundYield 14.8%

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 4-(7-(6-chloropyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide (Example 130, Step B, 78 mg, 0.197 mmol), lithium bis(trimethylsilyl)amide (LHMDS, 0.433 mL, 0.433 mmol, 1M in hexanes), and Pd2(dba3) (9.02 mg, 0.00985 mmol), was added P,P-dicyclohexyl(3-(2-N, N-dimethylaminophenyl)-phenyl)phosphine (7.75 mg, 0.0197 mmol). The mixture was sparged with nitrogen for 2 minutes, and then heated to 80° C. for 18 hours. After cooling to room temperature, 2N aqueous HCl (0.5 mL) was added and stirring was continued for 1 hour at room temperature. The mixture was partitioned between dichloromethane (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with dichloromethane (2×2 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC plate (1 mm thickness, Rf=0.45) eluting with 15% MeOH/CHCl3. The product was obtained as a beige, waxy solid (11 mg, 12%). 1H NMR (400 MHz, 1:1 CDCl3/CD3OD) δ 8.44 (d, J=5 Hz, 1H), 7.84-7.95 (m, 6H), 7.41 (m, 1H), 6.71 (d, J=9 Hz, 1H), 6.63 (d, J=5 Hz, 1H), 2.97 (s, 3H).

Workup

  1. customThe mixture was sparged with nitrogen for 2 minutes
  2. temperatureAfter cooling to room temperature
  3. addition2N aqueous HCl (0.5 mL) was added
  4. customThe mixture was partitioned between dichloromethane (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was re-extracted with dichloromethane (2×2 mL)
  7. dry with materialThe combined organic phases were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was purified by preparative TLC plate (1 mm thickness, Rf=0.45)
  11. washeluting with 15% MeOH/CHCl3

Sources & evidence

ORD record
ord-8af6619f44be44ebaa66710f6b5a455e
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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