Hydrochloric Acid → (E)-3-(8-({[4-(tert-Butyl)-1,3-thiazol-2-yl]amino}carbonyl)-2-{3-[(dimethylamino)-carbonyl]piperidino}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoic acid

HRID 1828478Notes

Reaction equation

HRID 1828478 reaction equation
[C:1]([C:5]1[N:6]=[C:7]([NH:10][C:11]([C:13]2[CH:40]=[CH:39][N:16]3[C:17](=[O:38])[C:18](/[CH:32]=[CH:33]/[C:34]([O:36]C)=[O:35])=[C:19]([N:21]4[CH2:26][CH2:25][CH2:24][CH:23]([C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH2:22]4)[N:20]=[C:15]3[CH:14]=2)=[O:12])[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>CO>[C:1]([C:5]1[N:6]=[C:7]([NH:10][C:11]([C:13]2[CH:40]=[CH:39][N:16]3[C:17](=[O:38])[C:18](/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35])=[C:19]([N:21]4[CH2:26][CH2:25][CH2:24][CH:23]([C:27]([N:29]([CH3:30])[CH3:31])=[O:28])[CH2:22]4)[N:20]=[C:15]3[CH:14]=2)=[O:12])[S:8][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide3×HCID 86588111methyl (E)-3-(8-({[4-(tert-butyl)-1,3-thiazol-2-yl]amino}carbonyl)-2-{3-[(dimethylamino)carbonyl]piperidino}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoate2×

Product 1

HCID 86588113(E)-3-(8-({[4-(tert-Butyl)-1,3-thiazol-2-yl]amino}carbonyl)-2-{3-[(dimethylamino)-carbonyl]piperidino}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The methyl (E)-3-(8-({[4-(tert-butyl)-1,3-thiazol-2-yl]amino}carbonyl)-2-{3-[(dimethylamino)carbonyl]piperidino}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoate (63.7 mg, 0.11 mmol) obtained in (C) was dissolved in methanol (10 ml), added dropwise with 1 N aqueous sodium hydroxide (562.0 μl, 0.56 mmol), and stirred at room temperature for 1 hour. The reaction solution was further added with 1 N aqueous sodium hydroxide (5.62 ml, 5.62 mmol), stirred at room temperature for 2 hours, further added with 1 N aqueous sodium hydroxide (2.81 ml, 2.81 mmol), and stirred at room temperature for 3 hours. The reaction solution was adjusted to about pH 2 with 1 N hydrochloric acid aqueous solution and extracted with chloroform/methanol (10:1, v/v). The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by preparative TLC (chloroform:methanol=20:1, v/v) and lyophilized from dioxane to obtain the title compound (37.6 mg, 38.5%, for the three steps) as yellow orange powder.

Workup

  1. stirringstirred at room temperature for 2 hours
  2. stirringstirred at room temperature for 3 hours
  3. extractionextracted with chloroform/methanol (10:1
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated
  7. customThe residue was purified by preparative TLC (chloroform

Sources & evidence

ORD record
ord-326a673e39df4b2d94f329235eca2ab6
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

Loading…