Hydrochloric Acid → HCID 67348795, compound

HRID 1676250Notes

Reaction equation

HRID 1676250 reaction equation
C(N(CC)[CH2:4][C:5]#[C:6][C:7]1[S:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[O:16][C:17]2[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=2[F:24])[CH:8]=1)C.Cl.O1CCOCC1>[Pd].C(Cl)Cl.CCO>[F:24][C:18]1[CH:19]=[C:20]([NH2:21])[CH:22]=[CH:23][C:17]=1[O:16][C:13]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:8]=[C:7]([CH2:6][CH2:5][CH3:4])[S:15][C:14]=12

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67346706HCID 67346706, compound

Product 1

HCID 67348795HCID 67348795, compoundYield 9.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584144Dichloromethane ethanolSolvent

Procedure

Obtained as a by-product during hydrogenation of the alkyne of 4-(2-(3-(diethylamino)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline (Example 6, Step B). A mixture of N-4-(2-(3-(diethylamino)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorobenzenamine (Example 6, Step B; 106 mg, 0.287 mmol), 4N HCl in dioxane (72 μL, 0.29 mmol), palladium on carbon (61 mg, 0.029 mmol; Degussa type, 10 wt % Pd. 50% water), and 1:1 CH2Cl2/EtOH (10 mL) was purged with N2 (3×), and then shaken under H2 (50 psi) for 18 hours at room temperature on a Parr shaker. The mixture was filtered, rinsing the Pd/C with MeOH. The resulting filtrate was concentrated, and the residue was partitioned between EtOAc (20 mL) and a saturated aqueous solution of NaHCO3 (20 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (25% MeOH in CH2Cl2). The product was obtained as a waxy solid (8 mg, 8%). 1H NMR (400 MHz, CDCl3) δ 8.41 (m, 1H), 7.23 (s, 1H, overlaps with chloroform), 7.03 (m, 1H), 6.52 (m, 3H), 3.81 (br s, 2H), 2.93 (m, 2H), 1.80 (m, 2H), 1.03 (m, 3H).

Workup

  1. customwas purged with N2 (3×)
  2. filtrationThe mixture was filtered
  3. washrinsing the Pd/C with MeOH
  4. concentrationThe resulting filtrate was concentrated
  5. customthe residue was partitioned between EtOAc (20 mL)
  6. customThe phases were separated
  7. extractionthe aqueous phase was re-extracted with EtOAc (2×10 mL)
  8. washThe combined organic phases were washed with brine (10 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude was purified by preparative TLC (25% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-331b5b3da05b45b19dcad0d9e3217769
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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