Hydrochloric Acid → HCID 44539323, compound

HRID 63502Notes

Reaction equation

HRID 63502 reaction equation
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[CH2:26]([O:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]=[C:36]=[O:37])=[CH:31][CH:30]=1)[CH3:27].C(N(CC)CC)C.Cl>CN(C)C=O>[O:25]=[C:19]1[CH:18]([N:12]2[CH2:11][C:10]3[C:14](=[CH:15][CH:16]=[C:8]([CH2:7][NH:6][C:36]([NH:35][C:32]4[CH:33]=[CH:34][C:29]([O:28][CH2:26][CH3:27])=[CH:30][CH:31]=4)=[O:37])[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 122887Benzene, 1-ethoxy-4-isocyanato-HCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Product 1

HCID 44539323HCID 44539323, compoundYield 108%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.50 g, 1.40 mmol) and 4-ethoxyphenylisocyanate (0.20 mL, 1.40 mmol) in N,N-dimethylformamide (10 mL), was added triethylamine (0.38 mL, 2.7 mmol) at room temperature under nitrogen. After 2 h, 1 N aq. HCl (15 mL) was added and the solids were isolated by filtration, washed with water (30 mL). The crude solids were slurried in EtOAc (15 mL) for 4 h then filtered, washed with EtOAc (15 mL) and dried in vacuo to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(4-ethoxy-phenyl)-urea as an off-white solid (0.66 g, 100% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 to 90/10 CH3CN/0.1% H3PO4 gradient over 15 mins, 7.43 min (99.34%); mp: 277-279° C.; 1H NMR (DMSO-d6) δ 1.29 (t, J=7.0 Hz, 3H, CH3), 1.85-2.14 (m, 1H, CHH), 2.23-2.47 (m, 1H, CHH), 2.59 (d, J=17.6 Hz, 1H, CHH), 2.79-3.07 (m, 1H, CHH), 3.94 (q, J=7.0 Hz, 2H, CH2), 4.23-4.36 (m, 1H, CHH), 4.36-4.55 (m, 3H, CHH, CH2), 5.11 (dd, J=4.9, 13.2 Hz, 1H, CH), 6.62 (t, J=5.9 Hz, 1H, NH), 6.80 (d, J=8.9 Hz, 2H, Ar), 7.29 (d, J=8.9 Hz, 2H, Ar), 7.44 (d, J=7.9 Hz, 1H, Ar), 7.51 (s, 1H, Ar), 7.69 (d, J=7.7 Hz, 1H, Ar), 8.40 (s, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.72, 22.49, 31.20, 42.79, 47.10, 51.56, 63.04, 114.44, 119.52, 121.85, 122.91, 126.88, 130.25, 133.39, 142.36, 145.03, 153.24, 155.44, 167.96, 170.99, 172.86; LCMS: MH=437; Anal Calcd for C23H24N4O5: C, 63.29; H, 5.54; N, 12.84. Found: C, 63.27; H, 5.46; N, 12.73.

Workup

  1. customthe solids were isolated by filtration
  2. washwashed with water (30 mL)
  3. waitThe crude solids were slurried in EtOAc (15 mL) for 4 h
  4. filtrationthen filtered
  5. washwashed with EtOAc (15 mL)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-e4b383627d0f416792874043b17b5bd0
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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