Indomethacin → N,N'-Dicyclohexylurea

HRID 379089Notes

Reaction equation

HRID 379089 reaction equation
[CH2:1]1[CH2:6][CH2:5][CH:4]([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:3][CH2:2]1.ClC1C=CC(C(N2C3C(=CC(OC)=CC=3)C(CC(O)=O)=C2C)=[O:24])=CC=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:10]1([NH:9][C:8](=[O:24])[NH:7][CH:4]2[CH2:3][CH2:2][CH2:1][CH2:6][CH2:5]2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

5

Reactant 2

HCID 3715IndomethacinHCID 10868Dicyclohexylcarbodiimide

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

DCC (1.0 g, 4.84 mmol) was added to a stirred solution of the product of Example 13d (0.9 g, 4.40 mmol), 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetic acid (1.57 g, 4.40 mmol), and DMAP (0.05 g) in CH2Cl2 (30 mL) at room temperature. The resulting suspension was stirred for 1 hour at room temperature. The precipitate was removed by filtration and washed with CH2Cl2 (25 mL). The filtrate was concentrated to give a green oil which was chromatographed on silica gel eluting with 5:95 MeOH:CH2Cl2 to afford a green solid (contaminated with dicyclohexyl urea). The solid was triturated with hexane (50 mL) and filtered. The filtrate was concentrated to give the title compound (1.85 g, 77%) as a viscous green oil. 1H NMR (300 MHz, CDCl3) δ 7.47-7.65 (mult, 4H), 6.84-6.91 (mult, 2H), 6.65 (dd, J=2.5 and 9.0 Hz, 1H), 4.29 (t, J=6.7 Hz, 2H), 3.81 (s, 3H), 3.61 (s, 2H), 2.35 (s, 3H), 2.27 (s, 3H), 2.10-2.70 (mult, 10H); 13C NMR (75 MHz, CDCl3) δ 170.5, 168.2, 156.1, 139.2, 135.9, 133.9, 131.1, 130.7, 130.6, 129.1, 114.9, 112.2, 111.6, 101.3, 61.3, 57.5, 55.7, 51.4 (2C), 46.1, 36.6, 30.3, 13.3; mass spectrum (API-TIS) m/z 544 (M+H).

Workup

  1. customThe precipitate was removed by filtration
  2. washwashed with CH2Cl2 (25 mL)
  3. concentrationThe filtrate was concentrated
  4. customto give a green oil which
  5. customwas chromatographed on silica gel eluting with 5:95 MeOH

Sources & evidence

ORD record
ord-34e1950e5692451aae96aa4c8add0aaf
Source dataset
uspto-grants-2001_10
Patent number
US06297260B1

Reaction notes

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