Acetic Acid → 2-[6-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indol-3-ylmethyl]-1,2,3,4-tetrahydro-benzo[4,5]thieno[3,2-c]pyridine formate

HRID 1947513Notes

Reaction equation

HRID 1947513 reaction equation
[S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[CH:2]1.[CH2:10]1[C:15]2[C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[S:18][C:14]=2[CH2:13][CH2:12][NH:11]1.C=O.[C:25]([OH:28])(=[O:27])[CH3:26].[O:29]1[CH2:34][CH2:33]OCC1>>[CH:25]([OH:28])=[O:27].[S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:29][C:34]1[CH:33]=[C:4]2[C:9]([C:25]([CH2:26][N:11]3[CH2:12][CH2:13][C:14]4[S:18][C:17]5[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=5[C:15]=4[CH2:10]3)=[CH:2][NH:3]2)=[CH:8][CH:7]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 312751,4-DioxaneHCID 113559561,2,3,4-Tetrahydro-benzo[4,5]thieno[3,2-c]pyridineHCID 20059202[1,3]Thiazolo[4,5-b]pyridine

Product 1

HCID 687729322-[6-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indol-3-ylmethyl]-1,2,3,4-tetrahydro-benzo[4,5]thieno[3,2-c]pyridine formateYield 56%

Conditions

Temperature
50 °C

Procedure

To a solution of thiazolo[4,5-b]pyridine (50 mg, 0.19 mmol) in dioxane (0.9 mL) was added 1,2,3,4-tetrahydro-benzo[4,5]thieno[3,2-c]pyridine (35 mg, 0.19 mmol), formaldehyde (35% wt in water, 14 μL, 15 mg, 0.19 mmol) and acetic acid (0.9 mL). The reaction mixture was heated (50° C., 16 h). The reaction mixture was cooled (rt) and concentrated in vacuo. The resulting residue was purified reverse phase HPLC to provide the title compound as a white solid (49 mg, 56%). MS (ESI): mass calcd. for C26H20N4OS2, 468.1; m/z found, 469.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 8.49 (dd, J=4.9, 1.6, 1H), 8.25 (dd, J=8.0, 1.6, 1H), 7.86 (d, J=8.6, 1H), 7.78 (d, J=7.8, 1H), 7.51 (d, J=7.9, 1H), 7.49-7.44 (m, 2H), 7.36-7.30 (m, 2H), 7.30-7.24 (m, 1H), 7.11 (dd, J=8.6, 2.2, 1H), 4.08 (s, 2H), 3.84 (s, 2H), 3.07-2.92 (m, 4H).

Workup

  1. temperatureThe reaction mixture was cooled (rt)
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified reverse phase HPLC

Sources & evidence

ORD record
ord-7b03c1d102284e09b8f8c4e538c5bf72
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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