Hydrochloric Acid → 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

HRID 712334Notes

Reaction equation

HRID 712334 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH3:40])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20](B(O)O)[C:21]4[S:25][C:24]([N:26]5[CH2:31][N:30]([CH3:32])[CH2:29][N:28]([CH2:33][CH3:34])[C:27]5=[O:35])=[N:23][C:22]=4[CH:36]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH:41]OS([O-])=O.[K+].Cl>CC(C)=O.C(=O)([O-])O.[Na+].O.CCOC(C)=O>[CH2:33]([N:28]1[CH2:29][N:30]([CH3:32])[CH2:31][N:26]([C:24]2[S:25][C:21]3[C:20]([OH:41])=[CH:19][C:18]([C:15]4[CH:14]=[N:13][C:12]([N:9]5[CH2:10][CH2:11][C:6]([CH3:40])([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8]5)=[N:17][CH:16]=4)=[CH:36][C:22]=3[N:23]=2)[C:27]1=[O:35])[CH3:34]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 23707502Potassium hydroxy sulfiteHCID 66976948[5-[2-(4-Ethoxycarbonyl-4-methyl-1-piperidyl)pyrimidin-5-yl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-7-yl]boronic acid2×

Product 1

HCID 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-carboxylateYield 117.2%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

[5-[2-(4-Ethoxycarbonyl-4-methyl-1-piperidyl)pyrimidin-5-yl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-7-yl]boronic acid (Intermediate 12) (1.88 g, 3.32 mmol) was dissolved in acetone (60 mL) and cooled to 0° C. Oxone (2.45 g, 3.98 mmol), dissolved in sodium hydrogen carbonate (sat aq) (40 mL), was added dropwise to the reaction mixture, resulting in a dark red solution. After addition, the mixture was stirred for 5 min at 0° C. before 1M HCl was added, bring the reaction mixture to ˜pH 2. The reaction mixture was diluted with water (100 mL) and EtOAc (100 mL). The organic layer was removed, and the aqueous layer was extracted twice more with EtOAc (2×100 mL). The organic fractions were dried and concentrated in vacuo to give a dark brown solid. Flash chromatography (40 g silica column), eluting with 0-100% EtOAc gradient in n-heptane, gave desired product (2.1 g, dark red solid). 1H NMR (MeOD) δ 8.61 (s, 2H), 7.41 (d, J=1.4 Hz, 1H), 6.84 (d, J=1.5 Hz, 1H), 5.21 (s, 2H), 4.47-4.36 (m, 4H), 4.28-4.20 (m, 2H), 3.53-3.44 (m, 2H), 3.35-3.25 (m, 2H, obscured under solvent), 2.67 (s, 3H), 2.19 (d, J=13.5 Hz, 2H), 1.56-1.46 (m, 2H), 1.36-1.21 (m, 9H). MS: [M−H]− 538.1.

Workup

  1. additionwas added dropwise to the reaction mixture
  2. customresulting in a dark red solution
  3. additionAfter addition
  4. additionwas added
  5. customThe organic layer was removed
  6. extractionthe aqueous layer was extracted twice more with EtOAc (2×100 mL)
  7. customThe organic fractions were dried
  8. concentrationconcentrated in vacuo
  9. customto give a dark brown solid
  10. washFlash chromatography (40 g silica column), eluting with 0-100% EtOAc gradient in n-heptane

Sources & evidence

ORD record
ord-5939c0e84e304be2b0f13683a1e8d6b9
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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