Acetic Acid → HCID 178454095, compound

HRID 532530Notes

Reaction equation

HRID 532530 reaction equation
[NH:1]1[C:5]2[CH2:6][NH:7][CH2:8][C:4]=2[CH:3]=[N:2]1.[C:9]([O:13][C:14](=[O:31])[NH:15][C@H:16]1[CH2:21][C:20](=O)[CH2:19][S:18][C@@H:17]1[C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[F:30])([CH3:12])([CH3:11])[CH3:10].C(N(CC)CC)C.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1.C([O-])(O)=O.[Na+]>CC(N(C)C)=O.C(OCC)(=O)C>[F:30][C:24]1[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=1[CH:17]1[C@@H:16]([NH:15][C:14](=[O:31])[O:13][C:9]([CH3:11])([CH3:10])[CH3:12])[CH2:21][C@@H:20]([N:7]2[CH2:8][C:4]3[C:5](=[N:1][NH:2][CH:3]=3)[CH2:6]2)[CH2:19][S:18]1

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 10943091HCID 10943091, compoundHCID 121362282HCID 121362282, compound2×

Product 1

HCID 178454095HCID 178454095, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

The bis-toluenesulfonic acid salt of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole (48 mg, 0.169 mmol) was dissolved in dry DMA (1.2 mL), tert-butyl[(2R,3S)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-thiopyran-3-yl]carbamate (Intermediate 2) (17.3 mg, 0.05 mmol) and triethylamine (65 μL, 0.469 mmol) were added and the solution was stirred at RT for 10 min. Acetic acid (43 μL, 0.75 mmol) was added and the solution was stirred at room temperature for 5 min and then transferred to a 50 degree oil bath. After 5 min, 1M sodium cyanoborohydride in THF (190 μL, 0.19 mmol) was added. After 30 min, the solution was cooled to room temperature and added to a mixture of ethyl acetate (30 mL) and saturated aqueous NaHCO3 (10 mL). The organic phase was washed with water (2×10 mL), brine (1×5 mL), dried with MgSO4., filtered and evaporated to an oil. Examination of the crude oil by HNMR showed an approximately 4:1 ratio of diastereomeric amines at C-5. The oil was purified by 1×500 micron preparative thin layer chromatography using 15:1 methylene chloride/10% ammonium hydroxide in EtOH as developing solvent. The more polar band was removed, eluted with the developing solvent mixture and evaporated to give the title compound.

Workup

  1. stirringthe solution was stirred at room temperature for 5 min
  2. customtransferred to a 50 degree
  3. waitAfter 5 min
  4. waitAfter 30 min
  5. temperaturethe solution was cooled to room temperature
  6. washThe organic phase was washed with water (2×10 mL), brine (1×5 mL)
  7. dry with materialdried with MgSO4
  8. filtration, filtered
  9. customevaporated to an oil
  10. customThe oil was purified by 1×500 micron preparative thin layer chromatography
  11. customThe more polar band was removed
  12. washeluted with the developing solvent mixture
  13. customevaporated

Sources & evidence

ORD record
ord-ab7ae3e134c24574acce0e8dc3baf78f
Source dataset
uspto-grants-2014_10
Patent number
US08853212B2

Reaction notes

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