Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate → 1-[5-[2-(Ethylcarbamoylamino)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712336Notes

Reaction equation

HRID 712336 reaction equation
[CH2:1]([N:3]1CN(C)C[N:5]([C:10]2[S:11][C:12]3[C:18]([O:19][CH3:20])=[CH:17][C:16]([C:21]4[CH:22]=[N:23][C:24]([N:27]5[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([O:35]CC)=[O:34])[CH2:29][CH2:28]5)=[N:25][CH:26]=4)=[CH:15][C:13]=3[N:14]=2)[C:4]1=[O:39])[CH3:2]>[OH-].[Na+].C1COCC1>[CH2:1]([NH:3][C:4]([NH:5][C:10]1[S:11][C:12]2[C:18]([O:19][CH3:20])=[CH:17][C:16]([C:21]3[CH:22]=[N:23][C:24]([N:27]4[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([OH:35])=[O:34])[CH2:29][CH2:28]4)=[N:25][CH:26]=3)=[CH:15][C:13]=2[N:14]=1)=[O:39])[CH3:2]

Participants

4

Reactant 1

HCID 66976917Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 1

HCID 866640441-[5-[2-(Ethylcarbamoylamino)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acidYield 31.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent4×

Procedure

Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (225 mg, 0.41 mmol) was dissolved in a mixture of NaOH (1M) (1 mL) and THF (3 mL) and the mixture stirred at rt for 3 hrs. A further portion of NaOH (1M) (1 mL) was added and stirring at rt continued for a further 1 hr. The reaction was heated at 60° C. for 16 hrs then at 100 C for 2 hrs and then with a further portion of NaOH (1 M, 1 mL) for 4 hrs. 5 M NaOH solution (1 mL, 5 mmol) was added and stirring continued at rt overnight, followed by 60° C. for 2 hrs. The reaction mixture was concentrated by freeze-drying then purified using reverse-phase chromatography (C18 column), eluting with 20-60% ACN gradient in water (with 0.1% formic acid), to give Compound 200 (60 mg, light yellow solid). 1H NMR (MeOD) δ 8.63 (s, 2H), 7.43 (s, 1H), 6.94 (s, 1H), 4.45-4.35 (m, 2H), 4.05 (s, 3H), 3.46-3.35 (m, 4H, obscured by solvent), 2.23-2.16 (m, 2H), 1.53-1.42 (m, 2H), 1.28 (s, 3H), 1.24 (t, J=7.2 Hz, 3H). [M+H]+471.1.

Workup

  1. stirringstirring at rt
  2. waitcontinued for a further 1 hr
  3. temperatureThe reaction was heated at 60° C. for 16 hrs
  4. waitat 100 C for 2 hrs
  5. stirringstirring
  6. waitcontinued at rt overnight
  7. waitfollowed by 60° C. for 2 hrs
  8. concentrationThe reaction mixture was concentrated
  9. customby freeze-drying
  10. customthen purified
  11. washeluting with 20-60% ACN gradient in water (with 0.1% formic acid)

Sources & evidence

ORD record
ord-0bb8fc650159475c9fd2538b81237e51
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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