Lithium Hydroxide → 4-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid

HRID 605357Notes

Reaction equation

HRID 605357 reaction equation
C[O:2][C:3](=[O:37])[C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:13][CH:12]=2)=[C:6]([NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH3:36])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:5]=1.[Li+].[OH-]>C1COCC1>[C:21]([O:20][C:18]([NH:17][C:14]1[CH:13]=[CH:12][C:11]([S:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:37])=[O:2])=[CH:5][C:6]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH3:36])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:16][CH:15]=1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 670403334-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester

Product 1

HCID 670407424-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acidYield 93.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester (1.50 g, 2.9 mmol) in THF (15 mL) was added aqueous LiOH [prepared from LiOH monohydrate (0.39 g, 9.0 mmol) and H2O (3.9 mL)] dropwise at room temperature. The mixture was stirred at room temperature for 21 hours. Additional aqueous LiOH solution [prepared from LiOH monohydrate (0.25 g) and H2O (2.5 mL)] was added at room temperature. The mixture was mixture was stirred at room temperature for 24 hours, and then evaporated. The aqueous mixture was diluted with 50 mL of H2O, washed with AcOEt, and treated with active charcoal. The mixture was filtered and the filtrate was carefully acidified to pH 4-5 with 1N HCl under stirring. The mixture (including oily precipitate) was sonicated for 1 hour and stirred at room temperature for 1 hour to give pale yellow solid. The resulting solid was collected by filtration, washed with H2O, and dried at 60° C. overnight under reduced pressure to give the title compound as pale yellow crystal (1.36 g, 93%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.48 (s, 9H), 2.68 (s, 3H), 6.93 (d, J=8.5 Hz, 1H), 7.37 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.57 (d, J=8.5 Hz, 1H), 7.75 (br-d, J=8.5 Hz, 1H), 7.89 (br-s, 1H), 8.58 (s, 1H), 8.80 (d, J=8.5 Hz, 1H), 9.62 (s, 1H), 10.15 (s, 1H), 12.97 (br-s, 1H)

Workup

  1. stirringwas stirred at room temperature for 24 hours
  2. customevaporated
  3. additionThe aqueous mixture was diluted with 50 mL of H2O
  4. washwashed with AcOEt
  5. additiontreated with active charcoal
  6. filtrationThe mixture was filtered
  7. stirringunder stirring
  8. customThe mixture (including oily precipitate) was sonicated for 1 hour
  9. stirringstirred at room temperature for 1 hour
  10. customto give pale yellow solid
  11. filtrationThe resulting solid was collected by filtration
  12. washwashed with H2O
  13. customdried at 60° C. overnight under reduced pressure

Sources & evidence

ORD record
ord-5d32870244c74f2a850df58b80519756
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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