Nitrogen → HCID 71007245, compound

HRID 716177Notes

Reaction equation

HRID 716177 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][S:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:10]1)([O-])=O.[In].[NH4+].[Cl-].N#N>CCO>[NH2:1][C:4]1[CH:5]=[N:6][S:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:10]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 25517Ammonium ChlorideHCID 5359967IndiumHCID 71007093HCID 71007093, compound

Product 1

HCID 71007245HCID 71007245, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

tert-butyl ((3S)-1-(4-amino-5-isothiazolyl)-3-piperidinyl) carbamate. A 30 mL Bohdan microwave vessel was charged with tert-butyl ((3S)-1-(4-nitro-5-isothiazolyl) -3-piperidinyl)carbamate (672 mg, 2.05 mmol), EtOH (11 mL), indium powder (963 mg, 8.39 mmol, Aldrich), 4.1 M aqueous NH4Cl (4.99 mL, 20.46 mmol) and a stirbar. The vessel was swept with N2, and crimped with a PTFE-lined seal. The vessel was placed into a 120° C. heat transfer block for 1.5 h. The vessel was briefly cooled, and de-pressurized by inserting a 25 gauge needle through the PTFE septa. The crimp-seal was removed, and the slurry was N2-pressure filtered warm through a 10 mL Bohdan glass frit fitted with a 0.22 μm PTFE, 25 mm syringe filter unit (Millipore, SLFG025NK). The solids were washed with hot EtOH (3×5 mL), and discarded. The filtrate and washes were combined and concentrated under a stream of N2. The residue was suspended in H2O (50 mL), and extracted with CHCl3 (5×20 mL). The combined extracts were washed with H2O (2×20 mL), and treated with MgSO4. The resulting slurry was vacuum filtered through a fine glass frit. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (9/1 CHCl3/THF) to afford tert-butyl ((3S)-1-(4-amino-5-isothiazolyl)-3-piperidinyl)-carbamate (536 mg, 1.80 mmol, 88% yield). MS (ESI, pos. ion) m/z: 299.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (s, 9 H) 1.48-1.56 (m, 1 H) 1.67-1.79 (m, 1 H) 1.79-1.92 (m, 2 H) 2.76 (dd, J=11.05, 7.14 Hz, 1 H) 2.85-2.95 (m, 1 H) 2.95-3.05 (m, 1 H) 3.18-3.47 (m, 3 H) 3.84 (br. s., 1 H) 4.82 (br. s., 1 H) 8.02 (s, 1 H).

Workup

  1. customlined seal
  2. customwas placed into a 120° C.
  3. temperatureheat transfer block for 1.5 h
  4. temperatureThe vessel was briefly cooled
  5. customThe crimp-seal was removed
  6. filtrationfiltered
  7. temperaturewarm through a 10 mL Bohdan glass frit
  8. customfitted with a 0.22 μm PTFE, 25 mm syringe
  9. filtrationfilter unit (Millipore, SLFG025NK)
  10. washThe solids were washed with hot EtOH (3×5 mL)
  11. concentrationconcentrated under a stream of N2
  12. extractionextracted with CHCl3 (5×20 mL)
  13. washThe combined extracts were washed with H2O (2×20 mL)
  14. additiontreated with MgSO4
  15. filtrationfiltered through a fine glass frit
  16. concentrationThe filtrate was concentrated in vacuo
  17. customThe residue was purified by silica gel chromatography (9/1 CHCl3/THF)

Sources & evidence

ORD record
ord-695dc6fa285a4705b51ca5ef393e9f14
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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