Dimethylamine → HCID 10414009, compound

HRID 346914Notes

Reaction equation

HRID 346914 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:34])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH:31]([F:33])[F:32])[CH:21]=1)[CH2:16][C:17](O)=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2].[C:35](N1C=CN=C1)([N:37]1C=CN=[CH:38]1)=O.CNC.O>O1CCCC1>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:34])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH:31]([F:32])[F:33])[CH:21]=1)[CH2:16][C:17]([N:37]([CH3:38])[CH3:35])=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 21082334HCID 21082334, compound

Product 1

HCID 10414009HCID 10414009, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(4-acetylamino-1 ,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3,4-bis-difluoromethoxy-phenyl)-propionic acid (350 mg, 0.72 mmol) in tetrahydrofurane was added carbonyldiimidazole (175 mg, 1.08 mmol) at room temperature. The solution was stirred for 2 hours at room temperature. To the mixture was added dimethylamine in THF (0.73 ml, 1.45 mmol). The resulted mixture was stirred at room temperature for 2 hours. Water (5 ml) was added to the reaction mixture. THF was removed in vacuo and the resulted mixture was taken up in ethyl acetate (20 ml). The organic layer was washed with saturated sodium bicarbonate solution (3×10 ml), water (10 ml), brine (10 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The resulted oil was purified by HPLC (acetonitrile:water=45:55) to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3,4-bis-difluoromethoxy-phenyl)-N,N-dimethyl-propionamide as a white solid (200 mg, 55%): mp, 83–85° C.; 1HNMR (CDCl3): 2.25 (s, 3H, CH3CO), 2.91 (s, 3H, NCH3), 3.06–3.13 (m, 4H, CHHCO+NCH3), 3.85 (dd, J=10, 15 Hz, 1H, CHHCO), 5.85–5.91 (m, 1H, CHN), 6.80 (t, JH-F=75 Hz, 1H, OCF2H), 6.84 (t, JH-F=75 Hz, 1H, OCF2H), 7.23 (d, J=7.5 Hz, 1H, Ar), 7.41–7.47 (m, 3H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 8.72 (d, J=7.5 Hz, 1H, Ar), 9.51 (s, 1H, NHCO). 13C NMR (CDCl3): 24.8, 34.5, 35.4, 36.9, 50.5, 111.4, 111.5, 115.2, 115.6, 115.7, 117.9, 119.8, 119.9, 122.0, 122.4, 124.7, 126.1, 131.1, 135.8, 137.4, 138.2, 141.9, 142.2, 167.7, 168.8, 169.1, 169.7; Anal. Calcd. for C23H21F4N3O6: C, 54.02; H, 4.14; N, 8.22. Found: C, 53.89; H, 3.88; N, 8.13.

Workup

  1. stirringThe resulted mixture was stirred at room temperature for 2 hours
  2. customTHF was removed in vacuo
  3. washThe organic layer was washed with saturated sodium bicarbonate solution (3×10 ml), water (10 ml), brine (10 ml)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe resulted oil was purified by HPLC (acetonitrile:water=45:55)

Sources & evidence

ORD record
ord-121d7a4348c04f72bc2bfae21f41dd42
Source dataset
uspto-grants-2007_02
Patent number
US07173058B2

Reaction notes

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