Lithium Hydroxide → 2-(4-(6-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)acetic acid

HRID 922368Notes

Reaction equation

HRID 922368 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:32])[NH:6][C:7]([C:15]1[N:20]=[C:19]([N:21]3[CH2:26][CH2:25][N:24]([CH2:27][C:28]([O:30]C)=[O:29])[CH2:23][CH2:22]3)[CH:18]=[CH:17][CH:16]=1)=[N:8]2.[OH-].[Li+]>C1COCC1.O.CO>[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:32])[NH:6][C:7]([C:15]1[N:20]=[C:19]([N:21]3[CH2:22][CH2:23][N:24]([CH2:27][C:28]([OH:30])=[O:29])[CH2:25][CH2:26]3)[CH:18]=[CH:17][CH:16]=1)=[N:8]2

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 136248835Methyl 2-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)acetate

Product 1

HCID 1362488422-(4-(6-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)acetic acidYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)acetate (0.156 g, 0.35 mmol) in THF (10 mL), water (5 mL) and methanol (3 mL) was added lithium hydroxide (0.043 g, 1.77 mmol). The reaction was stirred for 2 h at rt. After that time the reaction was cooled to rt, concentrated under reduced pressure, diluted with water (5 mL) and acidified with 1N HCl to pH 4.5-5.0. The precipitated solids were collected by filtration, washed with water and dried under high vacuum to give 2-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)acetic acid (0.135 g, 91%) as a yellow solid: mp 225° C. dec.; 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 7.72-7.79 (m, 1H), 7.67-7.72 (m, 1H), 7.07 (d, J=8.59 Hz, 1H), 6.78 (d, J=1.56 Hz 1H), 6.58 (d, J=1.56 Hz, 1H) 3.91 (s, 3H), 3.86 (s, 3H), 3.63-3.74 (m, 4H), 3.23 (s, 2H), 2.65-2.74 (m, 4H); ESI MS m/z 426 [M+H]+.

Workup

  1. temperatureAfter that time the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (5 mL)
  4. filtrationThe precipitated solids were collected by filtration
  5. washwashed with water
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-1fe1a73833ab4036979b3fb1bc52aeba
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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