Acetic Anhydride → HCID 21094208, compound

HRID 729725Notes

Reaction equation

HRID 729725 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([CH2:24][CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[C:14]([NH:16][C:17]3[S:18][C:19]([CH:22]=O)=[CH:20][N:21]=3)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH2:31]O.Cl.CC(OC(C)=O)=O>N1C=CC=CC=1>[C:22]([C:19]1[S:18][C:17]([NH:16][C:14](=[O:15])[CH:13]([C:10]2[CH:11]=[CH:12][C:7]([S:4]([CH:1]3[CH2:3][CH2:2]3)(=[O:5])=[O:6])=[CH:8][CH:9]=2)[CH2:24][CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[N:21][CH:20]=1)#[N:31]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 21093985HCID 21093985, compound

Product 1

HCID 21094208HCID 21094208, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

A stirred solution of 2-(4-cyclopropanesulfonylphenyl)-N-(5-formylthiazol-2-yl)-3-(tetrahydropyran-4-yl)propionamide (EXAMPLE 86, 369 mg, 0.82 mmol) in pyridine (1.53 mL) was treated with H2NOH.HCl (63 mg, 0.91 mmol) at 0° C. The mixture was stirred at 20° C. for 3 h, before being warmed up to 60° C. and treated with Ac2O (155 μL, 1.65 mmol). After 3 h, the mixture was cooled to 20° C., before being concentrated in vacuo and treated with CH2Cl2 (6 mL) and H2O (6 mL). The aqueous phase was acidified to pH 3 with 10% aqueous citric acid. The organic layer was separated, then the aqueous layer was further extracted with CH2Cl2 (2×10 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated to give a residue that was purified by column chromatography (IH-EtOAc, 1:3) to furnish the title compound: RTA=3.40 min; m/z (ES+)=487.4 [M+MeCN+H]+.

Workup

  1. temperaturebefore being warmed up to 60° C.
  2. waitAfter 3 h
  3. temperaturethe mixture was cooled to 20° C.
  4. concentrationbefore being concentrated in vacuo
  5. additiontreated with CH2Cl2 (6 mL) and H2O (6 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was further extracted with CH2Cl2 (2×10 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a residue that
  12. customwas purified by column chromatography (IH-EtOAc, 1:3)

Sources & evidence

ORD record
ord-84969a848a50438bba6820ada579fe53
Source dataset
uspto-grants-2009_09
Patent number
US07582632B2

Reaction notes

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