Sodium Hydroxide → HCID 86664048, compound

HRID 712340Notes

Reaction equation

HRID 712340 reaction equation
[CH2:1]([C:3]1([C:33]([O:35]CC)=[O:34])[CH2:8][CH2:7][N:6]([C:9]2[N:14]=[CH:13][C:12]([C:15]3[CH:16]=[C:17]([CH2:30][O:31][CH3:32])[C:18]4[S:22][C:21]([NH:23][C:24](=[O:28])[NH:25][CH2:26][CH3:27])=[N:20][C:19]=4[CH:29]=3)=[CH:11][N:10]=2)[CH2:5][CH2:4]1)[CH3:2].[OH-].[Na+]>CCO.O>[CH2:1]([C:3]1([C:33]([OH:35])=[O:34])[CH2:8][CH2:7][N:6]([C:9]2[N:10]=[CH:11][C:12]([C:15]3[CH:16]=[C:17]([CH2:30][O:31][CH3:32])[C:18]4[S:22][C:21]([NH:23][C:24](=[O:28])[NH:25][CH2:26][CH3:27])=[N:20][C:19]=4[CH:29]=3)=[CH:13][N:14]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 86664047HCID 86664047, compound

Product 1

HCID 86664048HCID 86664048, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(methoxymethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate (23 mg, 0.042 mmol) was dissolved in EtOH (1 mL) and 2M aqueous NaOH (330 μL, 0.66 mmol) added. The reaction mixture was stirred at 70° C. for 15 mins before additional 2M NaOH (670 μL, 1.34 mmol) was added and the reaction continued for 1.5 h then temperature increased to 100° C. and reaction continued for 4 h after which time the reaction was allowed to cool to rt overnight. After this time LCMS indicated small amount of starting material still present and the reaction was completed by heating to 100° C. for a further 2 h after which time the reaction was cooled to rt, diluted with water and extracted with DCM (3×). The aqueous layer was acidified with 10% HCl (aq) before extracting with EtOAc (3×) and the combined EtOAc extracts dried and the solvent evaporated to yield the Compound 203 (13.5 mg, 64%). 1H NMR (MeOD) δ 8.54 (s, 2H), 7.66 (bd, J=1.4 Hz, 1H), 7.28 (s, 1H), 4.68 (s, 2H), 4.48 (dt, J=13.7, 3.6 Hz, 2H), 3.35-3.28 (m, 2H), 3.22-3.11 (m, 2H), 2.20-2.13 (m, 2H), 1.60 (q, J=7.5 Hz, 2H), 1.44-1.34 (m, 2H), 1.21 (t, J=7.2 Hz, 3H), 0.89 (t, J=7.5 Hz, 3H). MS: 499.12 [M+H]+

Workup

  1. additionwas added
  2. customreaction
  3. waitcontinued for 4 h
  4. temperatureto cool to rt overnight
  5. temperatureby heating to 100° C. for a further 2 h after which time the reaction
  6. temperaturewas cooled to rt
  7. extractionextracted with DCM (3×)
  8. extractionbefore extracting with EtOAc (3×)
  9. dry with materialthe combined EtOAc extracts dried
  10. customthe solvent evaporated

Sources & evidence

ORD record
ord-4cee890e59af4dda8af968cb23f0b18e
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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