Carbon Tetrachloride → Tert-butyl (2-((tert-butyldimethylsilyl)oxy)-1-(5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)ethyl)carbamate

HRID 595514Notes

Reaction equation

HRID 595514 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C:11]([NH:13][NH:14][C:15](=O)[C:16]1[C:21]([NH:22][CH:23]([CH3:25])[CH3:24])=[CH:20][C:19]([Cl:26])=[N:18][CH:17]=1)=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.C(Cl)(Cl)(Cl)Cl>C(Cl)Cl>[Si:1]([O:8][CH2:9][CH:10]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:34])[CH3:32])[C:11]1[O:12][C:15]([C:16]2[CH:17]=[N:18][C:19]([Cl:26])=[CH:20][C:21]=2[NH:22][CH:23]([CH3:24])[CH3:25])=[N:14][N:13]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 131732604Tert-butyl (3-((tert-butyldimethylsilyl)oxy)-1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-1-oxopropan-2-yl)carbamate

Product 1

HCID 89697733Tert-butyl (2-((tert-butyldimethylsilyl)oxy)-1-(5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

tert-Butyl (3-((tert-butyldimethylsilyl)oxy)-1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-1-oxopropan-2-yl)carbamate (54) (100 mg, 0.18 mmol) in DCM (5 mL) was stirred at room temperature. Added triphenyl phosphine (0.56 mmol, 3 equiv.), Et3N (1.5 mol, 8 equiv.) and CCl4 (0.56 mmol, 3 equiv.). The reaction mixture was heated at 50° C. for 3 h. Reaction mixture was diluted using DCM. The DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography through silica gel and EtOAc:Pet. Ether as eluent to provide the desired compound, tert-butyl (2-((tert-butyldimethylsilyl)oxy)-1-(5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)ethyl)carbamate (55). LC/MS: Purospher@star RP-18, 4×55 mm, 3 μm; Solvent A=10% ACN: 90% H2O: 20 mM NH4OAc; Solvent B=90% ACN: 10% H2O: 20 mM NH4COOAc; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 2.567 min; LCMS (ES-API), m/z 512.3 (M+H).

Workup

  1. customReaction mixture
  2. additionwas diluted
  3. washThe DCM layer was washed with water
  4. customThe organic layer was collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography through silica gel and EtOAc

Sources & evidence

ORD record
ord-3d7bf64765424297813d085d278dabad
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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