Methanol → Ethyl 4-ethyl-1-(5-(2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate

HRID 712341Notes

Reaction equation

HRID 712341 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([C:22](=[O:25])[CH2:23][CH3:24])[C:10]2[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=2[CH:21]=1)(=O)=O.[CH3:28]O.[CH3:30][C:31]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:36][CH2:35][N:34]([C:37]2[N:42]=[CH:41][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][N:38]=2)[CH2:33][CH2:32]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1>[CH2:30]([C:31]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:32][CH2:33][N:34]([C:37]2[N:38]=[CH:39][C:40]([C:7]3[CH:8]=[C:9]([C:22](=[O:25])[CH2:23][CH3:24])[C:10]4[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=4[CH:21]=3)=[CH:41][N:42]=2)[CH2:35][CH2:36]1)[CH3:28]

Participants

6

Reactant 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 66976878Ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylateHCID 866640502-(3-Ethylureido)-7-propionylbenzo[d]thiazol-5-yl trifluoromethanesulfonate2×

Product 1

HCID 86664049Ethyl 4-ethyl-1-(5-(2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl trifluoromethanesulfonate (Intermediate 13) (0.25 g, 0.587 mmol) in 1,4-dioxane:MeOH (21 mL: 14 mL) were added ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate (0.46 g, 1.17 mmol) and potassium phosphate (0.19 g, 0.88 mmol) at rt under N2 atmosphere. The reaction mixture was degassed by N2 for 15 min followed by addition of tetrakis (triphenylphosphine)palladium(0) (0.068 g, 0.058 mmol). The reaction mixture was further degassed by N2 for 15 min then stirred for 2 h at 80° C. After the completion of reaction (by TLC), water (50 mL) was added, extracted with EtOAc (3×50 mL) and the combined organic layers washed with water, brine, dried over anhydrous Na2SO4, filtered then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 100-200 M, 70% EtOAc-hexane) to afford the desired product as an off-white solid (0.110 g, 35%). 1H NMR (DMSO-d6): δ 10.70 (br s, 1H), 8.87 (s, 2H), 8.23 (s, 1H), 8.14 (s, 1H), 6.80 (br s, 1H), 4.47 (m, 2H), 4.17 (q, J=7.20 Hz, 2H), 3.33 (m, 2H), 3.12-3.22 (m, 4H), 2.09 (m, 2H), 1.56 (q, J=7.60 Hz, 2H), 1.39 (m, 2H), 1.22 (t, J=7.20 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H), 1.10 (t, J=7.2 Hz, 3H) and 0.75 (t, J=7.2 Hz, 3H). MS: 539.52 [M+H]+

Workup

  1. customThe reaction mixture was degassed by N2 for 15 min
  2. customThe reaction mixture was further degassed by N2 for 15 min
  3. customAfter the completion of reaction (by TLC), water (50 mL)
  4. additionwas added
  5. extractionextracted with EtOAc (3×50 mL)
  6. washthe combined organic layers washed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationthen concentrated under reduced pressure
  10. customThe residue was purified by column chromatography (silica gel 100-200 M, 70% EtOAc-hexane)

Sources & evidence

ORD record
ord-252a85a64a594ef0bfc3697723709003
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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