Trifluoroacetic acid → 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

HRID 1014419Notes

Reaction equation

HRID 1014419 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([NH2:6])=[O:5].[Cl:12][C:13]1[N:14]=[C:15](Cl)[C:16]2[CH:21]=[CH:20][N:19]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:17]=2[N:18]=1.FC(F)(F)C(O)=O>C(O)C(F)(F)F>[Cl:12][C:13]1[N:14]=[C:15]([NH:1][C:2]2[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=2[C:4]([NH2:6])=[O:5])[C:16]2[CH:21]=[CH:20][N:19]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)(=[O:23])=[O:24])[C:17]=2[N:18]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 27789392-Amino-6-fluorobenzamideHCID 534868282,4-dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamideYield 55%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-6-fluorobenzamide (10 g, 64.9 mmol, Piedmont or Ryan Scientific) and 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (17.7 g, 51.7 mmol) was taken up into trifluoroethanol (400 mL) and trifluoroacetic acid (20 mL, 260 mmol). The resulting yellow slurry was heated at 80° C. After heating for 30 minutes a clear brown solution was obtained, which was heated at 80° C. for 18 h, then at the reflux temperature for an additional 6 h. The resulting slurry was cooled to 0° C. and filtered. The filtrate was concentrated down to 200 mL volume, heated at 80C for 20 h, cooled to 0° C., then filtered. The two crops of solids were combined, taken up into isopropanol (150 mL), heated at the reflux temperature for 4 h, then filtered to give 13 g (55%) of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a pale yellow solid; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (s, 3 H), 6.71 (d, J=3.66 Hz, 1 H), 7.12-7.17 (m, 1 H), 7.45-7.48 (m, 2 H), 7.49-7.52 (m, 1 H), 7.61 (d, J=7.87 Hz, 1 H), 7.67 (d, J=4.03 Hz, 1 H), 7.80 (s, 1 H), 7.89 (s, 1 H), 7.95-7.98 (m, 2 H), 10.47 (s, 1 H).

Workup

  1. temperatureAfter heating for 30 minutes a clear brown solution
  2. customwas obtained
  3. temperaturewhich was heated at 80° C. for 18 h
  4. temperatureThe resulting slurry was cooled to 0° C.
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated down to 200 mL volume
  7. temperatureheated at 80C for 20 h
  8. temperaturecooled to 0° C.
  9. filtrationfiltered
  10. temperatureheated at the reflux temperature for 4 h
  11. filtrationfiltered

Sources & evidence

ORD record
ord-8fd4810e9ded424ab2d1760b33975f37
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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