Hydrochloric Acid → 2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-thiadiazole

HRID 579322Notes

Reaction equation

HRID 579322 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:6]=[CH:5][C:4]=1[C:14]1[S:18][C:17]([C:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH:20]=2)=[N:16][N:15]=1.Cl>O1CCOCC1.CO>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:6]=[CH:5][C:4]=1[C:14]1[S:18][C:17]([C:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH:20]=2)=[N:16][N:15]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86727143tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 867271442-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-thiadiazoleYield 52.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (80 mg, 0.18 mmol) in 1,4-dioxane (1 mL) was added 4 M HCl in 1,4-dioxane (0.9 mL). The mixture was stirred for 1 h. The mixture was then diluted with MeOH, loaded on the SCX, washed with MeOH, eluted with 2 N NH3 in MeOH, and concentrated in vacuo. The residue was purified by column chromatography (CH2Cl2/MeOH) to give 32 mg of 2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-thiadiazole: HRMS (M+1) calcd. for C17H17N5OS 340.1232, found 340.1228; 1H NMR (400 MHz, DMSO-d6) δ 8.71 (d, J=2.53 Hz, 1H), 8.40 (d, J=8.59 Hz, 1H), 7.83 (d, J=1.52 Hz, 1H), 7.73 (d, J=2.02 Hz, 1H), 7.68 (dd, J=2.02, 8.59 Hz, 1H), 6.73 (m, 1H), 6.54-6.68 (m, 1H), 4.12 (s, 3H), 3.52 (m, 2H), 3.02 (t, J=5.81 Hz, 2H), 2.62 (m, 2H).

Workup

  1. washwashed with MeOH
  2. washeluted with 2 N NH3 in MeOH
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-e90f41e695d34131a92820bae6467802
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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