Hydrochloric Acid → HCID 86724075, compound

HRID 1748726Notes

Reaction equation

HRID 1748726 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][C:13](=O)[N:12]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:11]2[N:22]([CH3:31])[N:23]=[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)[C:10]1=2.B.C1COCC1.Cl.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][N:12]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:11]2[N:22]([CH3:31])[N:23]=[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)[C:10]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 86724072HCID 86724072, compound

Product 1

HCID 86724075HCID 86724075, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-[4-(2,4-dichlorophenyl)-1-methyl-7-oxo-3-(2-pyridyl)-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetate (1.18 g, 2.5 mmol, Preparation #9) in anhydrous THF (50 mL) was added a solution of borane THF complex (9.90 mL, 1M in THF, 4 mmol, Acros), the resulting mixture was stirred at rt for about 16 h and then for about 4 h at about 50° C. After cooling to about 4° C., 6 M aqueous HCl (10 mL) was added dropwise and the mixture stirred for about 45 min at rt. Subsequently, the mixture was cooled again to about 4° C., treated with 2 M aqueous NaOH (35 mL) and extracted with ethyl acetate (75 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/DCM 1:1 and ethyl acetate) to give methyl 2-[4-(2,4-dichlorophenyl)-1-methyl-3-(2-pyridyl)-6,7-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetate (0.65 g, 1.4 mmol, 56%) as a white foam, which was used as such: LC-MS (Table 1, Method d) Rt=2.90 min; m/z 463 (M+H)+

Workup

  1. waitfor about 4 h at about 50° C
  2. temperatureAfter cooling to about 4° C.
  3. stirringthe mixture stirred for about 45 min at rt
  4. temperatureSubsequently, the mixture was cooled again to about 4° C.
  5. extractionextracted with ethyl acetate (75 mL)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (SiO2, ethyl acetate/DCM 1:1 and ethyl acetate)

Sources & evidence

ORD record
ord-9f88b18615f543b1b6471bb4b81fa848
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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