Hydrochloric Acid → tert-Butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate

HRID 924505Notes

Reaction equation

HRID 924505 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:14]([N:15]2[CH:19]=[CH:18][N:17]=[N:16]2)[C@@H:13]([CH3:20])[CH2:12][N:11]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[N:27](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.O1CCOCC1.CCN(C(C)C)C(C)C.C(OC(ON1C(=O)CCC1=O)=O)(C)(C)C>>[NH2:27][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:21]=1[N:11]1[CH2:12][C@H:13]([CH3:20])[C@H:14]([N:15]2[CH:19]=[CH:18][N:17]=[N:16]2)[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 83168Carbonic acid, 1,1-dimethylethyl 2,5-dioxo-1-pyrrolidinyl esterHCID 86726945Di-tert-butyl {4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}imidodicarbonate

Product 1

HCID 86726946tert-Butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamateYield 74.2%

Procedure

To di-tert-butyl {4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}imidodicarbonate (77 mg, 0.13 mmol), 4.0 M HCl in dioxane (1.0 mL, 4.0 mmol) was added. After 1 h, the volatile solvents were removed under reduced pressure then the residue (HCl salt) was dried under high vacuum for 20 min. The residue was dissolved in DCM (0.9 mL) at 0° C. and DIPEA (0.35 mL, 2.0 mmol) and 1-[(tert-butoxycarbonyl)oxy]pyrrolidine-2,5-dione (28.9 mg, 0.134 mmol) were added. The mixture was stirred at room temperature for 90 min., then quenched with aq. NaHCO3 and diluted with EtOAc. The aqueous layer was separated and extracted with EtOAc (×2). The combined organic layers were dried, then concentrated under reduced pressure to give a yellow residue. The residue was purified by chromatography on silica using a CombiFlash® apparatus (0 to 25% MeOH in hexanes) to give the sub-title compound as a light yellow powder (36 mg, 72%). LCMS calc. for C18H28N7O2 (M+H)+: m/z=374.2. Found: 374.2.

Workup

  1. customthe volatile solvents were removed under reduced pressure
  2. dry with materialthe residue (HCl salt) was dried under high vacuum for 20 min
  3. dissolutionThe residue was dissolved in DCM (0.9 mL) at 0° C.
  4. customquenched with aq. NaHCO3
  5. additiondiluted with EtOAc
  6. customThe aqueous layer was separated
  7. extractionextracted with EtOAc (×2)
  8. customThe combined organic layers were dried
  9. concentrationconcentrated under reduced pressure
  10. customto give a yellow residue
  11. customThe residue was purified by chromatography on silica using a CombiFlash® apparatus (0 to 25% MeOH in hexanes)

Sources & evidence

ORD record
ord-f3022f24111d4b4f80fec939ce0c818b
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

Loading…