Acetic Acid → HCID 86670393, compound

HRID 1972539Notes

Reaction equation

HRID 1972539 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]([C:9]1[CH:10]=[N:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N+:30]([O-])=O)(=[O:23])=[O:22])[CH2:17][C@@H:16]2[CH3:33])=[N:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].CC(O)=O.CCO>CCOC(C)=O.[Pd]>[NH2:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[S:21]([N:18]1[CH2:19][CH2:20][N:15]([C:12]2[N:13]=[CH:14][C:9]([C:3]([OH:8])([C:2]([F:1])([F:34])[F:35])[C:4]([F:7])([F:6])[F:5])=[CH:10][N:11]=2)[C@@H:16]([CH3:33])[CH2:17]1)(=[O:22])=[O:23]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 86670392HCID 86670392, compound

Product 1

HCID 86670393HCID 86670393, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

Using a new 10% Pd/C CatCart cartridge (30 mm), a H-Cube/Gilson (Thalesnano Technology, Budapest, Hungary) system was purged with 1:1 0.5 M AcOH in EtOAc:EtOH. The CatCart was pre-saturated with H2 for 10 min (using the pre-saturate setting in the autosampler software program) at 0.5 mL/min. A solution of ((S)-1,1,1,3,3,3-hexafluoro-2-(2-(2-methyl-4-(2-nitrophenylsulfonyl)piperazin-1-yl)pyrimidin-5-yl)-2-propanol (0.21 g, 0.40 mmol) in 4.0 mL 1:1 0.5 M AcOH in EtOAc:EtOH was prepared. Three injections set at 1.5 mL were made, 30 mm 10% Pd/C CatCart, flow rate 0.5 mL/min, “1 bar” i.e., setting at “Full H2” on H-cube; temp 40° C.; 10 mL volume collected for each injection. The collected solution was concentrated and then dissolved in CH2Cl2. The solution was treated with saturated aqueous sodium bicarbonate then passed through a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) dried (Na2SO4), and then concentrated. The residue was then purification by silica gel chromatography (0 to 70% EtOAc/hexane) to afford (S)-2-(2-(4-(2-aminophenylsulfonyl)-2-methylpiperazin-1-yl)pyrimidin-5-yl)-1,1,1,3,3,3-hexafluoro-2-propanol (92 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.53 (s, 2H), 7.40 (dd, J=1.4, 8.2 Hz, 1H), 7.25-7.34 (m, 1H), 6.85 (d, J=7.8 Hz, 1H), 6.63 (t, J=7.1 Hz, 1H), 6.06 (s, 2H), 4.94 (br s, 1H), 4.57 (d, J=13.7 Hz, 1H), 3.75 (d, J=11.5 Hz, 1H), 3.51 (d, J=11.9 Hz, 1H), 3.10-3.27 (m, 1H), 2.60 (dd, J=3.7, 11.9 Hz, 1H), 2.38-2.47 (m, 1H), 1.10-1.22 (m, 3H). m/z (ESI, +ve ion) 499.9 (M+H)+. GK-GKRP IC50 (Binding)=0.508 μM; GK-GKRP EC50 (LC MS/MS-2)=0.516 μM.

Workup

  1. customa H-Cube/Gilson (Thalesnano Technology, Budapest, Hungary) system was purged with 1:1 0.5 M AcOH in EtOAc
  2. customtemp 40° C.
  3. custom10 mL volume collected for each injection
  4. concentrationThe collected solution was concentrated
  5. dissolutiondissolved in CH2Cl2
  6. additionThe solution was treated with saturated aqueous sodium bicarbonate
  7. customthen passed through a phase separation cartridge (Radleys Discovery Technologies, Essex, UK)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. custompurification by silica gel chromatography (0 to 70% EtOAc/hexane)

Sources & evidence

ORD record
ord-5edc0f4baf3f495a84e33905111c5684
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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