Lithium Hydroxide → 4-((5-Phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoic acid

HRID 2036787Notes

Reaction equation

HRID 2036787 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:23][CH2:24][C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][CH:26]=2)=[N:10][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[OH-]>CO.C1COCC1.O>[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:29]([OH:31])=[O:30])=[CH:33][CH:34]=2)=[N:10][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67055956Methyl 4-((5-phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoate

Product 1

HCID 670559474-((5-Phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoic acidYield 64.8%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of methyl 4-((5-phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoate (400 mg, 0.89 mmol) in MeOH-THF—H2O (6 mL-6 mL-0.5 mL) was added LiOH (112 mg, 2.67 mmol). Upon completion of addition, the reaction mixture was heated to 45° C. where it stirred for 12 h. After this time, the reaction mixture was concentrated under reduced pressure to remove the MeOH and THF and then carefully acidified with 1.5N HCl. The resulting precipitate was collected by filtration to afford 4-((5-phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoic acid (250 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.87 (bs, 1H), 9.68 (s, 2H), 9.39 (s, 1H), 8.09 (m, 1H), 7.98 (t, J=8.0 Hz, 1H), 7.86 (d, J=8.0 Hz, 2H), 7.53-7.48 (m, 6H), 7.26 (d, J=8.0 Hz, 2H), 6.65 (bs, 1H), 4.78 (d, J=5.2 Hz, 2H). LCMS Method O: retention time 1.73 min, [M+1]=434.2. HPLC Method B: purity 98.1%, retention time 8.24 min.

Workup

  1. additionUpon completion of addition
  2. concentrationAfter this time, the reaction mixture was concentrated under reduced pressure
  3. customto remove the MeOH and THF
  4. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-eb1aeb92c022451ea538cb1c620d3576
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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