Hydrochloric Acid → 1-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid

HRID 712261Notes

Reaction equation

HRID 712261 reaction equation
C([O:3][C:4]([C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH2:33][CH3:34])[C:21]4[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].Cl>CCO>[CH2:33]([C:20]1[C:21]2[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=2[CH:32]=[C:18]([C:15]2[CH:14]=[N:13][C:12]([N:9]3[CH2:10][CH2:11][C:6]([CH3:35])([C:4]([OH:5])=[O:3])[CH2:7][CH2:8]3)=[N:17][CH:16]=2)[CH:19]=1)[CH3:34]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 866639731-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 569522141-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acidYield 11.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

1-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester (19 mg) was dissolved in EtOH (1 mL) and 1 M aq NaOH (1 mL) added. The mixture was stirred at 70° C. overnight. The mixture was cooled to rt and acidified to pH 3 with 1 M HCl (aq) then concentrated in vacuo and the residue suspended (sonication) in ˜10% MeOH in DCM. The mixture was filtered through a syringe filter (20 micron) and the filtrate concentrated in vacuo. A cream solid was obtained (54 mg) and purified by preperative HPLC (Gilson, 40s-70-100% water/MeCN+0.1% formic acid). The relevant fractions were combined and concentrated in vacuo slightly then freeze-dried to give Compound 37 (2 mg) as a white solid. 1H NMR (CDCl3+CD3OD): δ 1.21 (3H, t, J=7.2 Hz), 1.25 (3H, s), 1.35 (3H, t, J=7.6 Hz), 1.45 (2H, m), 2.17 (2H, br d, J=13.6 Hz), 2.85 (2H, q, J=7.6 Hz), 3.32-3.41 (4H, m), 4.31 (2H, br dt, J=13.8 and 4.0 Hz), 7.14 (1H, s), 7.54 (1H, s), 8.54 (1H, s), 8.54 (1H, s). m/z: 469 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. concentrationthen concentrated in vacuo
  3. custom(sonication) in ˜10% MeOH in DCM
  4. filtrationThe mixture was filtered through a syringe
  5. filtrationfilter (20 micron)
  6. concentrationthe filtrate concentrated in vacuo
  7. customA cream solid was obtained (54 mg)
  8. custompurified by preperative HPLC (Gilson, 40s-70-100% water/MeCN+0.1% formic acid)
  9. concentrationconcentrated in vacuo slightly
  10. customfreeze-dried

Sources & evidence

ORD record
ord-e78e69b650b146eb8d55c369d9077620
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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