Hydrochloric Acid → 4-(4-Bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine

HRID 1748796Notes

Reaction equation

HRID 1748796 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][CH2:13][C:12](=O)[NH:11][C:10]3[N:16]([CH3:25])[N:17]=[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:9]2=3)=[C:4]([CH3:26])[CH:3]=1.B.C1COCC1.Cl.[OH-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][CH2:13][CH2:12][NH:11][C:10]3[N:16]([CH3:25])[N:17]=[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:9]2=3)=[C:4]([CH3:26])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 1363484514-(4-Bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one

Product 1

HCID 1363484254-(4-Bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (2.92 g, 6.8 mmol) in anhydrous THF (50 mL) was added a solution of borane THF complex (27.2 mL, 1M in THF, 27.2 mmol, Acros) at about 0° C. Subsequently, the mixture was stirred at rt, overnight. After cooling to about 0° C., HCl (5 M aq, 20 mL) was added dropwise and the mixture was stirred for about 30 min at rt, then the solution was brought to about pH=7 with 2 M aq NaOH, at about 0° C. The resulting mixture was extracted with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate) to give 4-(4-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e]-[1,4]thiazepine (2.1 g, 5.0 mmol, 74%) as an off white solid: LC-MS (Table 1, Method e) Rt=8.32 min, m/z 415 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.58 (3H, s) 2.69 (1H, ddd, J=15.0, 6.0, 2.0 Hz) 2.86 (1H, ddd, J=15.0, 9.0, 2.5 Hz) 3.21-3.31 (1H, m) 3.57-3.65 (1H, m) 3.79 (1H, br s) 3.83 (3H, s) 6.65 (1H, s) 7.04-7.09 (2H, m) 7.14 (1H, dd, J=8.5, 2.0 Hz) 7.31 (1H, d, J=2.0 Hz) 7.59 (1H, td, J=7.5, 2.0 Hz) 7.80 (1H, br.d, J=8.0 Hz) 8.45 (1H, br.d, J=5.0 Hz).

Workup

  1. temperatureAfter cooling to about 0° C.
  2. stirringthe mixture was stirred for about 30 min at rt
  3. extractionThe resulting mixture was extracted with ethyl acetate (200 mL)
  4. washThe organic layer was washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, ethyl acetate)

Sources & evidence

ORD record
ord-8487d251fad64ed39a034cc2cde33126
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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