Hydrochloric Acid → HCID 131730097, compound

HRID 2191093Notes

Reaction equation

HRID 2191093 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[CH:18]=[C:17]([C:19]3[C:23]4[CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][C:27](=[O:28])[C:22]=4[S:21][C:20]=3[N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:16]=[CH:15][N:14]=2)[CH:8]=1)(=O)=O.C(OC([NH:46][CH:47]1[CH2:51][CH2:50][NH:49][CH2:48]1)=O)(C)(C)C.CC(C)([O-])C.[K+].[ClH:58].CCOCC>O1CCOCC1.CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[ClH:58].[NH2:46][CH:47]1[CH2:51][CH2:50][N:49]([C:7]2[CH:8]=[C:9]([C:13]3[CH:18]=[C:17]([C:19]4[C:23]5[CH2:24][C:25]([CH3:29])([CH3:30])[CH2:26][C:27](=[O:28])[C:22]=5[S:21][C:20]=4[N:31]4[CH2:32][CH2:33][O:34][CH2:35][CH2:36]4)[CH:16]=[CH:15][N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH2:48]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 23665647Potassium tert-butoxideHCID 87571193HCID 87571193, compound

Product 1

HCID 131730097HCID 131730097, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 360 (100 mg, 0.18 mmol), 3-(tert-butoxycarbonylamino)-pyrrolidine (66 mg, 0.35 mmol), potassium tert-butoxide (28 mg, 0.25 mmol) and acetato(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium(II) (20 mg, 0.043 mmol) in 1,4-dioxane (2.0 mL) was heated in a sealed tube at 100° C., under microwave irradiation, for 2 h. The solvent was removed in vacuo and the residue was purified by column chromatography (SiO2, 0-100% EtOAc/heptane). The obtained solid was taken up in DCM (10 mL), treated with a solution of HCl in Et2O (2M, 1.0 mL, 2.0 mmol) and stirred at room temperature for 18 h. The solvent was removed in vacuo and the residue was purified by column chromatography (0-20% MeOH/DCM) to give the title compound (36 mg, 38%) as an orange solid. δH (CD3OD) 8.89-8.77 (1H, m), 8.57-8.44 (1H, m), 8.22-8.09 (1H, m), 7.62-7.51 (1H, m), 7.38-7.20 (2H, m), 7.02 (1H, d, J 7.7 Hz), 4.22-4.08 (1H, m), 3.93-3.48 (8H, m), 3.27-3.05 (4H, m), 2.81 (2H, s), 2.68-2.45 (3H, m), 2.38-2.21 (1H, m), 1.08 (6H, s). LCMS (ES+) 503.4 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by column chromatography (SiO2, 0-100% EtOAc/heptane)
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by column chromatography (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-4b5e6c2ad5bf4bfd8929b9b37284b596
Source dataset
uspto-grants-2012_12
Patent number
US08324204B2

Reaction notes

Loading…