Triethylamine → methyl 3-(4-(2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)propanoate

HRID 1429570Notes

Reaction equation

HRID 1429570 reaction equation
[CH:1]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[S:17][C:18]4[CH:24]=[C:23]([C:25]5[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=5)[CH:22]=[CH:21][C:19]=4[N:20]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[S:39]([CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])(=[O:41])=[O:40]>C(Cl)Cl>[CH:1]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[S:17][C:18]4[CH:24]=[C:23]([C:25]5[CH2:26][CH2:27][N:28]([S:39]([CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])(=[O:41])=[O:40])[CH2:29][CH:30]=5)[CH:22]=[CH:21][C:19]=4[N:20]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 4962888Methyl 3-(chlorosulfonyl)propanoateHCID 674682603-Isopropyl-5-(4-(6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazol-2-yloxy)piperidin-1-yl)-1,2,4-oxadiazole2×

Product 1

HCID 54596809methyl 3-(4-(2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)propanoateYield 58.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-isopropyl-5-(4-(6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazol-2-yloxy)piperidin-1-yl)-1,2,4-oxadiazole (Compound 43E, 95 mg, 0.223 mmol) and triethylamine (0.08 mL, 0.56 mmol) in CH2Cl2 (2 mL) at 0° C. was added methyl 3-(chlorosulfonyl)propanoate (62.5 mg, 0.335 mmol). The reaction mixture was stirred at 0° C. for 15 min, then at rt overnight. The reaction mixture was quenched with sat. aq. NaHCO3 (2 mL) and extracted with CH2Cl2 (3×3 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, CH2Cl2-EtOAc gradient 0 to 60% EtOAc) to afford methyl 3-(4-(2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)propanoate (75 mg, 0.13 mmol, 58% yield) as an off white solid. LCMS (m/z)=576 (M+H)+.

Workup

  1. customat rt
  2. customovernight
  3. customThe reaction mixture was quenched with sat. aq. NaHCO3 (2 mL)
  4. extractionextracted with CH2Cl2 (3×3 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (silica gel, CH2Cl2-EtOAc gradient 0 to 60% EtOAc)

Sources & evidence

ORD record
ord-7c64b47324bc400f82f695672563a51e
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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