Triethylamine → HCID 57730480, compound

HRID 63514Notes

Reaction equation

HRID 63514 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:7]2=[O:22].[C:23]([N:27]=[C:28]=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(CC)CC)C>C1COCC1>[C:23]([NH:27][C:28]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:7]2=[O:22])=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62412tert-Butyl isocyanateHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

Product 1

HCID 57730480HCID 57730480, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.00 g, 3.10 mmol) and t-butylisocyanate (0.31 g, 3.10 mmol) in THF (35 mL), was added triethylamine (0.88 mL, 6.20 mmol) at room temperature under nitrogen. The mixture was heated to 40° C. for 18 h then cooled to rt. The mixture was filtered and the filtrate diluted with EtOAc (100 mL). The organic layer was washed with dil. aq. HCl (100 mL), water (2×100 mL), dried (MgSO4) and concentrated. The crude product was purified by prep-HPLC (35/65 CH3CN/H2O). The product fractions were combined, concentrated and dried in vacuo to give 1-tert-butyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.40 g, 84% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.89 min (97.00%); mp: 202-204° C.; 1H NMR (DMSO-d6) δ 1.24 (s, 9H), 1.97-2.14 (m, 1H), 2.53-2.71 (m, 2H), 2.79-3.02 (m, 1H), 4.34 (d, J=5.9 Hz, 2H), 5.14 (dd, J=5.4, 12.9 Hz, 1H), 5.89 (s, 1H), 6.34 (t, J=6.0 Hz, 1H), 7.65-7.79 (m, 2H), 7.87 (d, J=7.7 Hz, 1H), 11.08 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 29.2, 30.9, 42.3, 48.9, 49.2, 121.4, 123.4, 129.5, 131.5, 133.0, 149.6, 157.3, 167.0, 167.2, 169.8, 172.7; Anal Calcd for C19H22N4O5+0.3H2O: C, 58.24; H, 5.81; N, 14.30. Found: C, 58.15; H, 5.52; N, 14.16.

Workup

  1. temperaturethen cooled to rt
  2. filtrationThe mixture was filtered
  3. additionthe filtrate diluted with EtOAc (100 mL)
  4. washThe organic layer was washed with dil. aq. HCl (100 mL), water (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by prep-HPLC (35/65 CH3CN/H2O)
  8. concentrationconcentrated
  9. customdried in vacuo

Sources & evidence

ORD record
ord-16116aea97254fe6a8cfc79280024c30
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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