Dimethylamine → HCID 11755695, compound

HRID 1797241Notes

Reaction equation

HRID 1797241 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:7]2[C:3]=1[CH2:4][N:5]([C@@H:18]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:19][C:20]([OH:22])=O)[C:6]2=[O:17].[C:34](N1C=CN=C1)([N:36]1C=CN=[CH:37]1)=O.CNC.O>O1CCCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:7]2[C:3]=1[CH2:4][N:5]([C@@H:18]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:19][C:20](=[O:22])[N:36]([CH3:37])[CH3:34])[C:6]2=[O:17]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 10457544HCID 10457544, compound

Product 1

HCID 11755695HCID 11755695, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (3R)-3-[4-chloro-7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-propionic acid (0.62 g, 1.3 mmol) in tetrahydrofurane (5 ml) was added carbonyldiimidazole (0.3 g, 2 mmol) at room temperature. The solution was stirred for 2 hours at room temperature. To the mixture was added THF solution of dimethylamine (2 M, 1.3 ml, 2.6 mmol). The resulted mixture was stirred at room temperature for 4 hrs. Water (20 ml) was added to the reaction mixture. THF was removed in vacuo and to the resulted mixture was added ethyl acetate (30 ml). The mixture was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml) and brine (20 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulted oil was stirred with ether (5 ml) for 2 hrs and filtered to give (1R)-cyclopropanecarboxylic acid {7-chloro-2-[2-dimethylcarbamoyl-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (0.5 g, 77%): mp 163–165° C.; 1HNMR (CDCl3): δ 0.86–0.89 (m, 2H, c-CH2), 1.08–1.11(m, 2H, c-CH2), 1.46 (t, J=7.5 Hz, 3H, OCH2CH3), 1.65–1.68 (m, 1H, c-CH), 2.93 (s, 3H, NCH3), 3.04 (dd, J=5, 16 Hz, 1H, CHH), 3.12 (s, 3H, NCH3), 3.56 (dd, J=5, 16 Hz, 1H, CHH), 3.86 (s, 3H, OCH3), 4.10 (q, J=7.5 Hz, 2H, OCH2CH3), 4.25 (d, J=17 Hz, 1H, NCHH), 4.60 (d, J=17 Hz, 1H, NCHH), 5.58–5.64 (m, 1H, CHN), 6.83–6.97 (m, 3H, Ar), 7.35 (d, J=9 Hz, 1H, Ar), 8.41 (d, J=9 Hz, 1H, Ar), 10.51 (s, 1H, NH); 13C NMR (CDCl3): 8.9, 15.4, 16.8, 36.2, 36.6, 38.0, 48.6, 54.3, 56.6, 65.2, 112.1, 113.1, 119.8, 120.0, 120.1, 122.3, 132.2, 133.2, 137.3, 139.9, 149.2, 149.8, 169.4, 170.1, 173.2; Anal. Calcd. for C26H30ClN3O5: C, 62.46; H, 6.05; N, 8.40. Found: C, 62.43; H, 5.42; N, 8.51.

Workup

  1. stirringThe resulted mixture was stirred at room temperature for 4 hrs
  2. customTHF was removed in vacuo and to the resulted mixture
  3. additionwas added ethyl acetate (30 ml)
  4. washThe mixture was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml) and brine (20 ml)
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. stirringThe resulted oil was stirred with ether (5 ml) for 2 hrs
  9. filtrationfiltered

Sources & evidence

ORD record
ord-cc6d7f58659b48ee80f0a3cd3123afb1
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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