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

HRID 1014476Notes

Reaction equation

HRID 1014476 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[NH2:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[C:24]=1[C:25]([OH:27])=[O:26].CCN(C(C)C)C(C)C>CC(O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][C:23]2[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[C:24]=2[C:25]([OH:27])=[O:26])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 146519722-Amino-4,6-difluorobenzoic acidHCID 534868282,4-dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 594416592-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzoic acidYield 38%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A slurry of 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (10 g, 29.2 mmol) and 2-amino-4,6-difluorobenzoic acid (source: Buttpark Ltd.) (5.06 g, 29.2 mmol) in iPrOH (250 ml) and DIPEA (25.5 ml, 146 mmol) was heated at 95° C. overnight, then distilled 180 mL of solvent off over 4 h, then heated for another 2 h. After allowing to cool to rt, the reaction mixture was diluted with EtOAc (300 mL), washed with a 1N HCl solution (400 mL), a saturated NaHCO3 solution (200 mL), a saturated NaCl solution (200 mL). The organic layer was diluted with Et2O (200 mL). The resulting slurry was filtered, the solid dried in vacuum oven overnight at 80° C. to obtain 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzoic acid as a pale yellow solid (5.3 g, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.37 (s, 3H), 6.60-6.78 (m, 2H), 7.48 (d, J=8.06 Hz, 2H), 7.77 (d, J=3.85 Hz, 1H), 7.98 (d, J=8.42 Hz, 2H), 8.23-8.36 (m, 1H); ESIMS (M+H)+=478.94.

Workup

  1. distillationdistilled 180 mL of solvent off over 4 h
  2. temperatureheated for another 2 h
  3. additionthe reaction mixture was diluted with EtOAc (300 mL)
  4. washwashed with a 1N HCl solution (400 mL)
  5. additionThe organic layer was diluted with Et2O (200 mL)
  6. filtrationThe resulting slurry was filtered
  7. customthe solid dried in vacuum oven overnight at 80° C.

Sources & evidence

ORD record
ord-ad783a4b25bc44efae840e918e6bfcbe
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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