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

HRID 883991Notes

Reaction equation

HRID 883991 reaction equation
C[O:2][C:3](=[O:39])[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]([CH:36]([CH3:38])[CH3:37])=[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:39])=[O:2])=[CH:5][C:6]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[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 HydroxideHCID 593768814-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester

Product 1

HCID 593768924-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acidYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester (3.25 g, 6.0 mmol) in THF (32.5 mL) was added aqueous LiOH [prepared from LiOH monohydrate (1.02 g, 24 mmol) and H2O (10 mL)] dropwise at room temperature. The mixture was stirred at room temperature for 26 hours, and then evaporated. The aqueous mixture was diluted with 100 mL of H2O, washed with AcOEt (50 mL), and then carefully acidified to pH 4-5 with 10% HCl at 5° C. under stirring. 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 (3.09 g, 98%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=7.0 Hz, 6H), 1.48 (s, 9H), 3.22 (septet, J=7.0 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 7.36 (d, J=8.8 Hz, 2H), 7.54 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.5 Hz, 1H), 7.75 (dd, J=8.5, 1.8 Hz, 1H), 7.89 (d, J=1.8 Hz, 1H), 8.58 (s, 1H), 8.84 (d, J=8.5 Hz, 1H), 9.61 (s, 1H), 10.16 (s, 1H), 12.98 (br-s, 1H)

Workup

  1. customevaporated
  2. additionThe aqueous mixture was diluted with 100 mL of H2O
  3. washwashed with AcOEt (50 mL)
  4. customcarefully acidified to pH 4-5 with 10% HCl at 5° C.
  5. stirringunder stirring
  6. filtrationThe resulting solid was collected by filtration
  7. washwashed with H2O
  8. customdried at 60° C. overnight under reduced pressure

Sources & evidence

ORD record
ord-06f71dd47a1a42f0955e9b45998aee94
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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