4-(Trifluoromethylthio)phenylacetic acid → HCID 57730504, compound

HRID 63428Notes

Reaction equation

HRID 63428 reaction equation
[F:1][C:2]([F:15])([F:14])[S:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=O)=[CH:6][CH:5]=1.Cl.[NH2:17][CH2:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[C:24](=[O:28])[N:23]([CH:29]1[CH2:34][CH2:33][C:32](=[O:35])[NH:31][C:30]1=[O:36])[CH2:22]2>CN(C=O)C>[O:36]=[C:30]1[CH:29]([N:23]2[CH2:22][C:21]3[C:25](=[CH:26][CH:27]=[C:19]([CH2:18][NH:17][C:11](=[O:13])[CH2:10][C:7]4[CH:6]=[CH:5][C:4]([S:3][C:2]([F:1])([F:15])[F:14])=[CH:9][CH:8]=4)[CH:20]=3)[C:24]2=[O:28])[CH2:34][CH2:33][C:32](=[O:35])[NH:31]1

Participants

4

Reactant 2

HCID 27779024-(Trifluoromethylthio)phenylacetic acidHCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 57730504HCID 57730504, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A stirred mixture of 4-(trifluoromethylthio)phenylacetic acid (0.38 g, 1.6 mmol), and CDI-(0.27 g, 1.7 mmol) in DMF (20 ml) was heated at 40° C. for 2 hrs. Then, 3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride (0.5 g, 1.6 mmol) was added to the mixture and allowed to stir for 3 h. The mixture was quenched with 4% aqueous HCl (30 mL). The precipitate was filtered and washed with H2O (50 mL) and dried in vacuo, providing N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-2-(4-trifluoromethylsulfanyl-phenyl)-acetamide as a white solid (0.36 g, 46% yield); mp 208-210° C.; HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 6.30 (98.81%); 1H NMR (DMSO-d6) δ 1.97-2.03 (m, 1H), 2.36-2.44 (m, 1H), 2.58-2.63 (m, 1H), 2.86-2.98 (m, 1H), 3.60 (s, 2H), 4.28 (d, 1H, J=17.4), 4.38-4.45 (m, 3H), 5.11 (dd, 1H, J=13.2, J=5.1), 7.38 (d, 1H, J=8.1), 7.44-7.46 (m, 3H), 7.65-7.68 (m, 3H), 8.75 (t, 1H, J=5.7), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 41.8, 42.3, 47.0, 51.5, 120.7 (q, J=1.9), 122.1, 122.9, 127.0, 129.6 (q, J=306), 130.4, 136.1, 140.2, 142.3, 143.6, 167.9, 169.5, 171.0, 172.9; LCMS: MH=492; Anal. Calcd for C23H20F3N3O4S+0.15H2O: C, 55.90; H, 4.14; N, 8.50. Found: C, 55.56; H, 4.09; N, 8.37.

Workup

  1. customThe mixture was quenched with 4% aqueous HCl (30 mL)
  2. filtrationThe precipitate was filtered
  3. washwashed with H2O (50 mL)
  4. customdried in vacuo

Sources & evidence

ORD record
ord-7ab88b4a7fd644e9983ad82bb4b2ab03
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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