Ethyl ketone → Ethyl 2-{(3S,4R)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylate

HRID 1425318Notes

Reaction equation

HRID 1425318 reaction equation
[CH3:1][CH2:2][C:3](=O)[CH2:4][CH3:5].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:21][C@@H:22]1[C@H:27]([NH:28][C:29]([C:31]2[NH:32][C:33]([CH2:37][CH3:38])=[C:34]([Cl:36])[N:35]=2)=[O:30])[CH2:26][CH2:25][N:24]([C:39]2[S:40][C:41]3[C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:46][CH:45]=[CH:44][C:42]=3[N:43]=2)[CH2:23]1.C(=O)(O)[O-].[Na+]>CO.O1CCCC1>[Cl:36][C:34]1[N:35]=[C:31]([C:29]([NH:28][C@@H:27]2[CH2:26][CH2:25][N:24]([C:39]3[S:40][C:41]4[C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:46][CH:45]=[CH:44][C:42]=4[N:43]=3)[CH2:23][C@@H:22]2[NH:21][CH:3]([CH2:4][CH3:5])[CH2:2][CH3:1])=[O:30])[NH:32][C:33]=1[CH2:37][CH3:38]

Participants

7

Reactant 4

HCID 7288Ethyl ketoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 67548804Ethyl 2-[(3S,4R)-3-amino-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}piperidin-1-yl]-1,3-benzothiazole-7-carboxylate

Product 1

HCID 67549801Ethyl 2-{(3S,4R)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Pentanone (68.9 μL, 0.65 mmol) and sodium triacetoxyborohydride (165 mg, 0.78 mmol) were added four times every two hours to a mixed solution of ethyl 2-[(3S,4R)-3-amino-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}piperidin-1-yl]-1,3-benzothiazole-7-carboxylate obtained in Example (202e) (62.0 mg, 0.13 mmol) in methanol (1 mL) and tetrahydrofuran (1 mL) under ice-cooling, and the mixture was stirred at room temperature for 15 hours. Saturated aqueous sodium bicarbonate solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluate: hexane:ethyl acetate=1:1 v/v) to obtain 48 mg of the title compound (68%) as a colorless solid.

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe insoluble matter was separated by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluate: hexane:ethyl acetate=1:1 v/v)

Sources & evidence

ORD record
ord-f568d16777bb466ea2e3915ef4f2a553
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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