Water → Ethyl 1-(5-(2-(3-ethylureido)-7-(pyridin-2-yl)benzo[d]thiazol-5-yl)pyridazin-3-yl)-4-methylpiperidine-4-carboxylate

HRID 712326Notes

Reaction equation

HRID 712326 reaction equation
Br[C:2]1[N:7]=[N:6][CH:5]=[C:4]([C:8]2[CH:9]=[C:10]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:11]3[S:15][C:14]([NH:16][C:17]([NH:19][CH2:20][CH3:21])=[O:18])=[N:13][C:12]=3[CH:22]=2)[CH:3]=1.CCN(CC)CC.Cl.[CH3:37][C:38]1([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.O>CN(C=O)C>[CH2:20]([NH:19][C:17](=[O:18])[NH:16][C:14]1[S:15][C:11]2[C:10]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[CH:9][C:8]([C:4]3[CH:3]=[C:2]([N:41]4[CH2:42][CH2:43][C:38]([CH3:37])([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:39][CH2:40]4)[N:7]=[N:6][CH:5]=3)=[CH:22][C:12]=2[N:13]=1)[CH3:21]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 19361804Ethyl 4-methylpiperidine-4-carboxylate hydrochlorideHCID 866639621-(5-(6-Bromopyridazin-4-yl)-7-(pyridin-2-yl)benzothiazol-2-yl)-3-ethylurea2×

Product 1

HCID 86664038Ethyl 1-(5-(2-(3-ethylureido)-7-(pyridin-2-yl)benzo[d]thiazol-5-yl)pyridazin-3-yl)-4-methylpiperidine-4-carboxylateYield 48.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(5-(6-bromopyridazin-4-yl)-7-(pyridin-2-yl)benzothiazol-2-yl)-3-ethylurea (Intermediate 10) (0.090 g, 0.19 mmol) in DMF (2 mL) was added Et3N (0.08 mL, 0.57 mmol) followed by the addition of ethyl 4-methylpiperidine-4-carboxylate hydrochloride (0.06 g, 0.29 mmol) and the mixture heated to 90° C. for 20 h then cooled to rt, water added and extracted with EtOAc (3×75 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 3% MeOH: DCM to obtain the desired product as yellow solid (0.05 g, 47%). MS: 546.40 [M+H]+.

Workup

  1. temperaturethen cooled to rt
  2. extractionextracted with EtOAc (3×75 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude residue was purified over 100-200 M silica-gel

Sources & evidence

ORD record
ord-67f04b1bdd1c4c92888373f3fa8aa1d0
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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