Sodium Hydroxide → 1-[5-[7-Bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712344Notes

Reaction equation

HRID 712344 reaction equation
[Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31]CC)=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[C:3]=1[O:35][CH3:36].[OH-].[Na+]>CCO>[Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:22]=[N:21][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([OH:31])=[O:30])[CH2:25][CH2:24]3)=[N:19][CH:18]=2)[C:3]=1[O:35][CH3:36]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86664051Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 1

HCID 866640521-[5-[7-Bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (47 mg, 0.081 mmol) was dissolved in EtOH (3 mL) and NaOH solution (1 mL, 1 M, aq) was added to give a pale yellow solution. The mixture was heated to 60° C. overnight then cooled to rt, the EtOH removed under reduced pressure and the residue acidified with HCl solution (1 M, aq) to pH 3. The mixture was extracted into EtOAc (3×15 mL) and the combined organic layer washed with brine, dried over Na2SO4 and concentrated to dryness under reduced pressure. The mixture was purified by chromatography, Biotage SP4, 4 g Si cartridge, 50-100% EtOAc in heptane. The relevant fractions were combined to give Compound 208 as an off white solid, 8 mg (18%). 1H NMR (CDCl3): δ 1.31 (3H, t, J=7.2 Hz), 1.42 (3H, s), 1.61 (2H, m), 2.27 (2H, m), 3.47 (2H, m), 3.64 (3H, s), 3.84 (2H, m), 4.15 (2H, q, J=7.2 Hz), 4.2-7.2 (3H, br s), 7.48 (1H, s), 8.62 (2H, s). MS: 549.07/551.06 [M+H]+.

Workup

  1. customto give a pale yellow solution
  2. temperaturethen cooled to rt
  3. customthe EtOH removed under reduced pressure
  4. extractionThe mixture was extracted into EtOAc (3×15 mL)
  5. washthe combined organic layer washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe mixture was purified by chromatography, Biotage SP4, 4 g Si cartridge, 50-100% EtOAc in heptane

Sources & evidence

ORD record
ord-61e3c0d5d67e4ebbb0b0f5b36135e4f8
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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