3-(Trifluoromethyl)phenyl isocyanate → HCID 24895849, compound

HRID 240677Notes

Reaction equation

HRID 240677 reaction equation
Cl.[CH3:2][NH:3][CH2:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH2:7][N:8]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:9]2=[O:14].[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([N:31]=[C:32]=[O:33])[CH:26]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:22]=[C:16]1[CH:15]([N:8]2[CH2:7][C:6]3[C:10](=[CH:11][CH:12]=[CH:13][C:5]=3[CH2:4][N:3]([CH3:2])[C:32]([NH:31][C:27]3[CH:28]=[CH:29][CH:30]=[C:25]([C:24]([F:34])([F:35])[F:23])[CH:26]=3)=[O:33])[C:9]2=[O:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 94833-(Trifluoromethyl)phenyl isocyanateHCID 81531DiisopropylethylamineHCID 67026973HCID 67026973, compound

Product 1

HCID 24895849HCID 24895849, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(4-methylaminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.60 g, 1.86 mmol) and α,α,α-trifluoro-m-tolyl-isocyanate (0.29 mL, 2.23 mmol) in dry CH2Cl2 (80 ml), was added diisopropylethylamine (0.45 mL g, 2.60 mmol). The mixture was stirred at room temperature overnight. The mixture was quenched with MeOH and filtered. The resulting solid was rinsed with CH2Cl2 (5 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-3-(3-trifluoromethyl-phenyl)-urea (0.58 g, 66%): mp 198-200° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=1.91 (98%); 1H NMR (DMSO-d6): δ 2.00-2.05 (m, 1H), 2.28-2.39 (m, 1H), 2.56-2.63 (m, 1H), 2.85-2.93 (m, 1H), 3.01 (s, 3H), 4.32-4.53 (dd, J=8, 20 Hz, 2H), 4.67 (s, 2H), 5.11-5.18 (dd, J=5.9, 15.8 Hz, 1H), 7.30 (d, J=7.5 Hz, 1H), 7.44-7.57 (m, 3H), 7.65 (d, J=7.5 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.94 (s, 1H), 8.81 (s, 1H), 11.02 (s, 1H). 13C NMR (DMSO-d6) δ: 22.56, 31.17, 34.76, 46.25, 48.36, 51.60, 115.71, 118.50, 121.78, 123.15, 126.42, 128.49, 128.83, 129.44, 129.81, 131.94, 133.59, 140.14, 141.33, 155.41, 168.00, 171.01, 172.82. Anal Calcd for C23H21F3N4O4: C, 58.23; H, 4.46; N, 11.81, F, 12.01. Found: C, 58.06; H, 4.30; N, 12.09, F, 11.59.

Workup

  1. customThe mixture was quenched with MeOH
  2. filtrationfiltered
  3. washThe resulting solid was rinsed with CH2Cl2 (5 mL)

Sources & evidence

ORD record
ord-2bf4d441170e4df38ee3c41cc567d6af
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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