Acetyl chloride → HCID 86664056, compound

HRID 712348Notes

Reaction equation

HRID 712348 reaction equation
[C:1]([C:3]1[C:11]2[S:10][C:9]([NH:12][C:13](=[O:17])[NH:14][CH2:15][CH3:16])=[N:8][C:7]=2[CH:6]=[C:5]([C:18]2[CH:19]=[N:20][C:21]([N:24]3[CH2:29][CH2:28][C:27]([CH3:35])([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH2:25]3)=[N:22][CH:23]=2)[CH:4]=1)#[N:2].Cl.[NH2:37]O.[C:39](Cl)(=[O:41])[CH3:40]>N1C=CC=CC=1.CCOC(C)=O>[CH2:15]([NH:14][C:13]([NH:12][C:9]1[S:10][C:11]2[C:3]([C:1]3[N:37]=[C:39]([CH3:40])[O:41][N:2]=3)=[CH:4][C:5]([C:18]3[CH:23]=[N:22][C:21]([N:24]4[CH2:29][CH2:28][C:27]([CH3:35])([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH2:25]4)=[N:20][CH:19]=3)=[CH:6][C:7]=2[N:8]=1)=[O:17])[CH3:16]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 443297Hydroxyamine hydrochlorideHCID 86664055HCID 86664055, compound

Product 1

HCID 86664056HCID 86664056, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 1-[5-[7-cyano-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (327 mg, 0.66 mmol) and hydroxylamine hydrochloride (230 mg, 3.31 mmol) were suspended in pyridine (20 mL) and the mixture stirred at 80° C. for 4 h. The reaction was cooled to rt and acetyl chloride (565 μL, 7.95 mmol) was added then stirred at 80° C. for 9 h. The reaction was diluted with EtOAc (100 mL), washed with dilute HCl (2×100 mL), brine and separated. The organic fraction was dried (Na2SO4) and concentrated under reduced pressure and the oily residue purified by flash column chromatography (40 g GraceResolv silica cartridge—dry loaded), eluting with 50-100% EtOAc/heptane to afford the desired compound (192 mg, 53%) as a white solid. MS: 551.13 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to rt
  2. stirringthen stirred at 80° C. for 9 h
  3. washwashed with dilute HCl (2×100 mL), brine
  4. customseparated
  5. dry with materialThe organic fraction was dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customthe oily residue purified by flash column chromatography (40 g GraceResolv silica cartridge—dry loaded)
  8. washeluting with 50-100% EtOAc/heptane

Sources & evidence

ORD record
ord-168371ab206a46beabec5a814dc28581
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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