2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 57845549, compound

HRID 734638Notes

Reaction equation

HRID 734638 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=[O:14].[CH:15]1([CH2:20][CH2:21][C:22]([NH:24][C:25]2[NH:26][CH:27]=[C:28]([C:33]3[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=3)[C:29]=2[C:30]([NH2:32])=[O:31])=[O:23])[CH2:19][CH2:18][CH2:17][CH2:16]1>O1CCCC1>[CH:15]1([CH2:20][CH2:21][C:22]([NH:24][C:25]2[NH:26][CH:27]=[C:28]([C:33]3[CH:34]=[CH:35][C:36]([NH:39][C:13]([NH:12][C:3]4[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=4[F:1])=[O:14])=[CH:37][CH:38]=3)[C:29]=2[C:30]([NH2:32])=[O:31])=[O:23])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 69059637HCID 69059637, compound

Product 1

HCID 57845549HCID 57845549, compoundYield 17.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

0.072 cm3 (0.50 mmol) of 2-fluoro-5-trifluoromethylphenyl isocyanate is added at a temperature in the region of 25° C. to 0.170 g (0.50 mmol) of 2-(3-cyclo-pentylpropionylamino)-4-(4-aminophenyl)-1H-pyrrole-3-carboxamide in solution in 20 cm3 of tetrahydrofuran. After stirring for 48 hours at a temperature in the region of 25° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa). The residue is then diluted in 50 cm3 of ethyl acetate and then washed with 50 cm3 of water and 50 cm3 of a saturated aqueous sodium chloride solution. The organic solution is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is purified by flash chromatography [eluent; dichloromethane/methanol/acetonitrile (95/2.5/2.5 by volume)]. After concentrating the fractions under reduced pressure, 0.048 g of 2-(3-cyclopentylpropionylamino)-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)-ureido]phenyl}-1H-pyrrole-3-carboxamide is obtained in the form of a yellow powder melting at 222° C. IR (KBr), 3470; 3389; 1717; 1633; 1594; 1546; 1443; 1341; 1312; 1194; 1167; 1119; 1070 & 614 cm−1. 1H NMR (400 MHz, (CD3)2SO, —δ in ppm) 1.11 (m, 2H); from 1.42 to 1.68 (m, 6H); from 1.71 to 1.85 (m, 3H); 2.40 (t, J=8.0 Hz, 2H); 5.56 (broad m, 1H); 6.39 (d, J=2.5 Hz, 1H); 7.09 (broad m, 1H); 7.30 (d, J=9.0 Hz, 2H); 7.38 (m, 1H); 7.49 (m partially masked, 1H); 7.51 (d, J=9.0 Hz, 2H); 8.62 (dd, J=2.5 and 7.5 Hz, 1H); 9.00 (broad s, 1H); 9.32 (broad s, 1H); 10.8 (broad s, 1H); 11.4 (broad s, 1H).

Workup

  1. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  2. additionThe residue is then diluted in 50 cm3 of ethyl acetate
  3. washwashed with 50 cm3 of water and 50 cm3 of a saturated aqueous sodium chloride solution
  4. dry with materialThe organic solution is dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customto give a residue which
  8. customis purified by flash chromatography [eluent; dichloromethane/methanol/acetonitrile (95/2.5/2.5 by volume)]
  9. concentrationAfter concentrating the fractions under reduced pressure

Sources & evidence

ORD record
ord-59761c0434e643aa87a6d2af67b2bba0
Source dataset
uspto-grants-2009_09
Patent number
US07592365B2

Reaction notes

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