Dimethylformamide → 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

HRID 712335Notes

Reaction equation

HRID 712335 reaction equation
[CH2:1]([N:3]1[CH2:8][N:7]([CH3:9])[CH2:6][N:5]([C:10]2[S:11][C:12]3[C:18]([OH:19])=[CH:17][C:16]([C:20]4[CH:21]=[N:22][C:23]([N:26]5[CH2:31][CH2:30][C:29]([CH3:37])([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH2:27]5)=[N:24][CH:25]=4)=[CH:15][C:13]=3[N:14]=2)[C:4]1=[O:38])[CH3:2].[C:39](=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.CI>[Cl-].[NH4+].CCOC(C)=O>[CH2:1]([N:3]1[CH2:8][N:7]([CH3:9])[CH2:6][N:5]([C:10]2[S:11][C:12]3[C:18]([O:19][CH3:39])=[CH:17][C:16]([C:20]4[CH:25]=[N:24][C:23]([N:26]5[CH2:27][CH2:28][C:29]([CH3:37])([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:30][CH2:31]5)=[N:22][CH:21]=4)=[CH:15][C:13]=3[N:14]=2)[C:4]1=[O:38])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodide2×HCID 10796Cesium carbonateHCID 66977323Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-hydroxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 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-carboxylateYield 68.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-hydroxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (533 mg, 0.593 mmol), dicesium carbonate (390 mg, 1.19 mmol) and N,N-dimethylformamide (10 mL) at 0° C. was added MeI (55 μL, 0.89 mmol) and the reaction mixture was allowed to warm to rt before stirring for 1 hr. A further portion of MeI (110 μL, 1.78 mmol) was added and the mixture stirred at rt for a further 18 hrs. The reaction was diluted with ammonium chloride solution (50 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer washed with further portions of EtOAc (2×50 mL). The organic layers were combined, dried (MgSO4) and concentrated in vacuo to give crude product mixture followed by flash chromatography (12 g silica column), eluting with 0-100% EtOAc gradient in n-heptane to give the desired product (226 mg, light brown solid). 1H NMR (CDCl3) δ 8.63 (s, 2H), 7.51 (d, J=1.3 Hz, 1H), 6.82 (d, J=1.3 Hz, 1H), 5.23 (s, 2H), 4.42 (dt, J=13.6, 4.0 Hz, 2H), 4.35 (s, 2H), 4.25 (q, J=7.1 Hz, 2H), 4.04 (s, 3H), 3.56-3.50 (m, 2H), 3.43-3.34 (m, 2H), 2.70 (s, 3H), 2.25 (d, J=13.6 Hz, 2H), 1.58-1.48 (m, 2H), 1.38-1.24 (m, 9H). MS: 554.1 [M+H]+.

Workup

  1. stirringthe mixture stirred at rt for a further 18 hrs
  2. customThe organic layer was separated
  3. washthe aqueous layer washed with further portions of EtOAc (2×50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give crude product mixture
  7. washeluting with 0-100% EtOAc gradient in n-heptane

Sources & evidence

ORD record
ord-0659bb893fa14484a3fa926c9d9a333c
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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