Hydrochloric Acid → HCID 136216249, compound

HRID 1748783Notes

Reaction equation

HRID 1748783 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][C:13]([CH3:16])([CH3:15])[C:12](=O)[NH:11][C:10]3[N:18]([CH3:24])[N:19]=[C:20]([CH:21]4[CH2:23][CH2:22]4)[C:9]2=3)=[C:4]([CH3:25])[CH:3]=1.O1CCCC1.B.Cl.[OH-].[Na+]>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][C:13]([CH3:15])([CH3:16])[CH2:12][NH:11][C:10]3[N:18]([CH3:24])[N:19]=[C:20]([CH:21]4[CH2:23][CH2:22]4)[C:9]2=3)=[C:4]([CH3:25])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 136348449HCID 136348449, compound

Product 1

HCID 136216249HCID 136216249, compoundYield 65.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-chloro-2-methyl-phenyl)-3-cyclopropyl-1,6,6-trimethyl-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (1.2 g, 3.19 mmol) in THF (20 mL) was added a solution of borane tetrahydro-furan complex (14 mL, 1M in THF, 4 mmol, Acros) at about 4° C. Subsequently, the mixture was stirred for about 18 h at rt. After cooling to about 4° C., HCl (5 M aqueous, 12 mL) was added dropwise and the mixture was stirred for about 2 h at about 4° C., then NaOH (1 M aq, 60 mL) and ethyl acetate (200 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with water (2×25 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1 to 100:0) to give 4-(4-chloro-2-methyl-phenyl)-3-cyclopropyl-1,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine as white solid (0.75 g, 2.1 mmol, 65%). LC-MS (Table 1, Method e) Rt=7.48 min, m/z: 362 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 0.38-0.65 (4H, m) 0.91-0.99 (1H, m) 1.01 (3H, s) 1.35 (3H, s) 2.52 (3H, s) 3.09 (1H, dd, J=14.5, 5.5 Hz) 3.40 (1H, dd, J=14.5, 5.0 Hz) 3.62 (3H, s) 3.65 (1H br.t.) 5.17 (1H, s) 7.07 (1H, dd, J=8.5, 2.0 Hz) 7.16 (1H, d, J=2.0 Hz) 7.21 (1H, d, J=8.5 Hz).

Workup

  1. temperatureAfter cooling to about 4° C.
  2. stirringthe mixture was stirred for about 2 h at about 4° C.
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
  5. washThe combined organic layers were washed with water (2×25 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1 to 100:0)

Sources & evidence

ORD record
ord-ee0ef3d3afbe4c4b86b7982fe5bb33be
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

Loading…