Lithium Hydroxide → 4-(4-Amino-3-fluorophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzoic acid

HRID 605425Notes

Reaction equation

HRID 605425 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][C:19]=2[NH:28][C:29]2[C:30]3[CH:38]=[CH:37][C:36]([CH:39]([CH3:41])[CH3:40])=[N:35][C:31]=3[N:32]=[CH:33][N:34]=2)[CH:5]=[CH:6][C:7]=1[NH:8]C(OCC(Cl)(Cl)Cl)=O.[Li+].[OH-]>C1COCC1>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([S:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][C:19]=2[NH:28][C:29]2[C:30]3[CH:38]=[CH:37][C:36]([CH:39]([CH3:40])[CH3:41])=[N:35][C:31]=3[N:32]=[CH:33][N:34]=2)=[CH:3][C:2]=1[F:1]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67040683Methyl 4-(3-fluoro-4-((2,2,2-trichloroethoxy)carbonylamino)phenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzoate

Product 1

HCID 670403594-(4-Amino-3-fluorophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzoic acidYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

The product of Example 449E (1.25 g, 2.0 mmol) in THF (12.5 mL) was reacted with aqueous LiOH solution [prepared from LiOH monohydrate (0.42 g, 10 mmol) and water (8.4 mL)] dropwise at room temperature. The mixture was stirred at 40° C. for 16 hours, and then concentrated. The aqueous mixture was diluted with 50 mL of water, washed with ethyl acetate (1×40 mL), and then carefully acidified to pH 5-6 with 1N HCl under stirring. After 30 minutes, the resulting precipitate was collected by filtration, washed with cold water, and dried at 40° C. for 3 days in vacuum to give the title compound as pale brown crystal (0.77 g, 87%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=7. 0 Hz, 6H), 3.23 (septet, J=7.0 Hz, 1H), 5.67 (s, 2H), 7.15-7.30 (m, 2H), 6.81 (dd, J=9.2, 8.4 Hz, 1H), 6.91 (d, J=8.4 Hz, 1H), 7.02 (dd, J=8.4, 1.8 Hz, 1H), 7.11 (dd, J=11.4, 1.8 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.76 (dd, J=8.4, 1.9 Hz, 1H), 7.86 (d, J=1.9 Hz, 1H), 8.57 (s, 1H), 8.85 (d, J=8.5 Hz, 1H), 10.12 (s, 1H). MS ESI+ m/z: 450 (M+H), ESI− m/z: 448 (M−H).

Workup

  1. concentrationconcentrated
  2. additionThe aqueous mixture was diluted with 50 mL of water
  3. washwashed with ethyl acetate (1×40 mL)
  4. stirringunder stirring
  5. waitAfter 30 minutes
  6. filtrationthe resulting precipitate was collected by filtration
  7. washwashed with cold water
  8. customdried at 40° C. for 3 days in vacuum

Sources & evidence

ORD record
ord-5234d26d0f4549f89f7e4424f62da4a0
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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