2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 57845580, compound

HRID 734634Notes

Reaction equation

HRID 734634 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].[C:15]([NH:20][C:21]1[NH:22][CH:23]=[C:24]([C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)[C:25]=1[C:26]([NH2:28])=[O:27])(=[O:19])[CH:16]([CH3:18])[CH3:17]>O1CCCC1>[C:15]([NH:20][C:21]1[NH:22][CH:23]=[C:24]([C:29]2[CH:30]=[CH:31][C:32]([NH:35][C:13]([NH:12][C:3]3[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=3[F:1])=[O:14])=[CH:33][CH:34]=2)[C:25]=1[C:26]([NH2:28])=[O:27])(=[O:19])[CH:16]([CH3:18])[CH3:17]

Participants

4

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 69056535HCID 69056535, compound

Product 1

HCID 57845580HCID 57845580, compoundYield 44.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

0.076 cm3 (0.436 mmol) of 2-fluoro-5-trifluoromethylphenyl isocyanate is added at a temperature in the region of 25° C. to 0.125 g (0.436 mmol) of 2-isobutyrylamino-4-(4-aminophenyl)-1H-pyrrole-3-carboxamide in solution in 15 cm3 of tetrahydrofuran. After stirring for 17 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 40 cm3 of ethyl acetate and then washed with 40 cm3 of water. 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 crystallized from 8 cm3 of a cyclohexane/ethyl acetate mixture (70/30 by volume). After filtration and drying, 0.096 g of 2-isobutyrylamino-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)-ureido]phenyl}-1H-pyrrole-3-carboxamide is obtained in the form of a cream solid melting at 196° C. IR (KBr), 3472; 3384; 1667; 1594; 1546; 1443; 1340; 1313; 1198; 1167; 1120; 1070; 937 & 614 cm−1. 1H NMR (400 MHz, (CD3)2SO, —δ in ppm), 1.17 (d, J=7.0 Hz, 6H); 2.61 (m, 1H); 5.62 (broad m, 1H); 6.40 (d, J=2.5 Hz, 1H); 7.00 (broad m, 1H); 7.30 (d, J=9.0 Hz, 2H); 7.39 (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); 8.99 (broad s, 1H); 9.32 (broad s, 1H); 10.95 (broad s, 1H); 11.45 (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 40 cm3 of ethyl acetate
  3. washwashed with 40 cm3 of water
  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 crystallized from 8 cm3 of a cyclohexane/ethyl acetate mixture (70/30 by volume)
  9. filtrationAfter filtration
  10. customdrying

Sources & evidence

ORD record
ord-138e48126022436586081de6c61eee63
Source dataset
uspto-grants-2009_09
Patent number
US07592365B2

Reaction notes

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