Potassium Hydroxide → 2-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-yl]-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide

HRID 631847Notes

Reaction equation

HRID 631847 reaction equation
O1C2C=CC(C([C:13]([CH:15](Br)[C:16]3[CH:25]=[CH:24][C:19]4[O:20][CH2:21][CH2:22][O:23][C:18]=4[CH:17]=3)=O)Br)=CC=2OCC1.[NH2:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[C:32](=[CH:33][CH:34]=[C:35]([C:40]([O:42]C)=O)[CH:36]=2)[CH2:31]1)=[S:29].Cl.[NH2:45][OH:46].[OH-].[K+]>O1CCOCC1.CO>[O:20]1[C:19]2[CH:24]=[CH:25][C:16]([C:15]3[N:27]=[C:28]([N:30]4[CH2:39][CH2:38][C:37]5[C:32](=[CH:33][CH:34]=[C:35]([C:40]([NH:45][OH:46])=[O:42])[CH:36]=5)[CH2:31]4)[S:29][CH:13]=3)=[CH:17][C:18]=2[O:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 58147281Methyl 2-(aminocarbonothioyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylateHCID 1317332281,4-Benzodioxan-6-ylbromomethyketone

Product 1

HCID 581471592-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-yl]-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamideYield 35%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1,4-benzodioxan-6-ylbromomethyketone (0.051 g, 0.2 mmol), methyl 2-(aminocarbonothioyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (0.05 g, 0 2 mmol) in 1,4-dioxane (1 mL) heated at 40° C. for 2 h. Upon cooling to room temperature, the solvent was removed under reduced pressure to afford a solid residue. To the solid residue was added hydroxylamine hydrochloride (0.056 g, 0.8 mmol), potassium hydroxide (0.09 g, 1.6 mmol), and methanol (2 mL). The mixture was heated at 80° C. for 2 h. Upon cooling to room temperature, the solvent was then removed under reduced pressure, the residue dissolved in DMSO (1 mL) and purified on Gilson prep-HPLC [236 nm, rt=7.54 min (12 min), 30-70% gradient MeCN-H2O] to give 28.6 mg (35%) of the title compound as a white solid. LCMS: (FA) ES+410; 1H NMR (MeOD, 400 MHz) δ 8.51 (s, 1 H), 7.60 (m, 2 H), 7.33 (m, 3 H), 6.82 (s, 2 H), 4.74 (m, 2 H), 4.25 (m, 4 H), 3.84 (m, 2 H), 3.08 (m, 2 H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customto afford a solid residue
  3. temperatureThe mixture was heated at 80° C. for 2 h
  4. temperatureUpon cooling to room temperature
  5. customthe solvent was then removed under reduced pressure
  6. dissolutionthe residue dissolved in DMSO (1 mL)
  7. custompurified on Gilson prep-HPLC [236 nm, rt=7.54 min (12 min), 30-70% gradient MeCN-H2O]

Sources & evidence

ORD record
ord-6d13afc2e0504987bb884d9bfc7e1356
Source dataset
uspto-grants-2016_04
Patent number
US09321731B2

Reaction notes

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