Hydrochloric Acid → HCID 59471685, compound

HRID 78654Notes

Reaction equation

HRID 78654 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[NH2:48][C:49]1[C:50]([C:67]2[O:71][C:70](=O)[NH:69][N:68]=2)=[N:51][C:52]([C:55]2[CH:60]=[CH:59][C:58]([S:61]([CH:64]([CH3:66])[CH3:65])(=[O:63])=[O:62])=[CH:57][CH:56]=2)=[CH:53][N:54]=1.Cl>CN(C=O)C.CS(C)=O.CCOC(C)=O.C(=O)([O-])O.[Na+]>[NH2:48][C:49]1[C:50]([C:67]2[O:71][C:70]([NH:10][CH:11]3[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)=[N:69][N:68]=2)=[N:51][C:52]([C:55]2[CH:60]=[CH:59][C:58]([S:61]([CH:64]([CH3:65])[CH3:66])(=[O:63])=[O:62])=[CH:57][CH:56]=2)=[CH:53][N:54]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5458091-BOC-3-AminopiperidineHCID 2733179PyBroPHCID 59472420HCID 59472420, compound

Product 1

HCID 59471685HCID 59471685, compoundYield 20.2%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

DIPEA (173.6 μL, 1.0 mmol), tert-butyl 3-aminopiperidine-1-carboxylate (99.7 mg, 0.50 mmol) and bromo(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (340.6 mg, 0.73 mmol) were added to a mixture of 5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-3H-1,3,4-oxadiazol-2-one (120 mg, 0.33 mmol) in DMF (600 μL) and DMSO (600 4). The resulting mixture was stirred at room temperature for 4.5 h. The reaction mixture was diluted with EtOAc (5 mL) and saturated aqueous sodium hydrogen carbonate solution (5 mL). The aqueous layer was washed with EtOAc (3×5 mL) and the combined organic extracts dried over MgSO4, filtered and concentrated in vacuo. The residue was taken up in methanol (1.2 mL) and HCl (332 μL, 1.0 mmol, 3M solution in methanol) and the resulting solution stirred at room temperature overnight. The reaction mixture was evaporated to dryness and the solid triturated with acetonitrile and then purified further by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]. The product fractions were passed through a bicarbonate cartridge and lypholised to give the title compound as a yellow solid (29.6 mg, 20%); H NMR (400.0 MHz, DMSO) d 1.19 (d, 6H), 1.43-1.48 (m, 2H), 1.64-1.67 (m, 1H), 1.99-2.01 (m, 1H), 2.40-2.46 (m, 2H), 2.77-2.80 (m, 1H), 3.10-3.14 (m, 1H), 3.46-3.55 (m, 2H), 7.80 (br s, 1H), 7.95 (d, 2H), 8.23 (t, 2H), 8.27 (s, 1H) and 8.89 (s, 1H) ppm; MS (ES+) 444.25

Workup

  1. washThe aqueous layer was washed with EtOAc (3×5 mL)
  2. dry with materialthe combined organic extracts dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe reaction mixture was evaporated to dryness
  6. customthe solid triturated with acetonitrile
  7. custompurified further by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-3bb11b41f1e244d9a9a25a6debd1e2c4
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

Loading…