Sodium Hydroxide → 3-(2-(3-(Benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoic acid hydrochloride

HRID 1426183Notes

Reaction equation

HRID 1426183 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]2[S:25][CH:26]=[C:27]([CH2:29][CH2:30][C:31]([O:33]C)=[O:32])[N:28]=2)=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[ClH:22].[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]2[S:25][CH:26]=[C:27]([CH2:29][CH2:30][C:31]([OH:33])=[O:32])[N:28]=2)=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59225711Methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate

Product 1

HCID 866397083-(2-(3-(Benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoic acid hydrochlorideYield 148.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate (Example 131; 0.315 g, 0.635 mmol), 1M aqueous sodium hydroxide (0.953 ml, 0.953 mmol), and methanol (6 mL) was heated at 65° C. for one hour. The reaction mixture was then cooled and partitioned between chloroform and saturated ammonium chloride, and the aqueous layer was extracted twice with chloroform. The combined organic layers were washed with brine, dried, and concentrated. The residue was dissolved in THF (2 mL) and ether (2 mL, and 1N HCl in ether (1.5 mL) was added. The mixture was stirred 5 minutes, and then hexanes (3 mL) were added. The solids were isolated by filtration to afford 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoic acid hydrochloride (0.245 g, 74.4% yield) as a white powder. 1H NMR (DMSO-d6) δ 2.64 (t, 2H), 2.87 (t, 3H), 5.32 (s, 2H), 6.81 (s, 1H), 6.99 (d, 1H), 7.21 (t, 1H), 7.31-7.43 (m, 4H), 7.47 (d, 1H), 7.55-7.66 (m, 4H).

Workup

  1. temperatureThe reaction mixture was then cooled
  2. custompartitioned between chloroform and saturated ammonium chloride
  3. extractionthe aqueous layer was extracted twice with chloroform
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in THF (2 mL)
  8. additionether (2 mL, and 1N HCl in ether (1.5 mL) was added
  9. additionhexanes (3 mL) were added
  10. customThe solids were isolated by filtration

Sources & evidence

ORD record
ord-7d232e7d126b4d4a96c112869af3734f
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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