Hydrochloric Acid → HCID 117701571, compound

HRID 1507452Notes

Reaction equation

HRID 1507452 reaction equation
[CH2:1]([O:8][C:9]1[C:18]([C:19]([NH:21][CH2:22][CH2:23][OH:24])=O)=[C:17]2[C:12]([C:13](=[O:36])[C:14]([CH3:35])=[C:15]([CH:25]3[CH2:30][CH2:29][N:28]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:27][CH2:26]3)[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.N12CCCN=C1CCCCC2.Cl>ClCCl.ClCCCl>[CH2:1]([O:8][C:9]1[C:18]([C:19]2[O:24][CH2:23][CH2:22][N:21]=2)=[C:17]2[C:12]([C:13](=[O:36])[C:14]([CH3:35])=[C:15]([CH:25]3[CH2:26][CH2:27][N:28]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:29][CH2:30]3)[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 117701715HCID 117701715, compound

Product 1

HCID 117701571HCID 117701571, compoundYield 27.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(benzyloxy)-N-(2-hydroxyethyl)-3-methyl-4-oxo-2-(1-propanoylpiperidin-4-yl)-4H-chromene-8-carboxamide (140 mg, 0.28 mmol) obtained in Example 35-2 in dichloromethane (4 mL), thionyl chloride (62 μL, 0.85 mmol) was added dropwise, and then the mixture was stirred at room temperature for 10 hours. The reaction solution was concentrated under reduced pressure, and then the residue was subjected to azeotropy with toluene (6 mL). 1,2-Dichloroethane (4 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (950 μL, 5.68 mmol) were added to the obtained residue, and then the mixture was heated to reflux for 4 days. A 0.2 N aqueous hydrochloric acid solution (50 mL) was added to the reaction solution, followed by extraction with dichloromethane. The organic layer was dried over sodium sulfate. The desiccant was filtered off, and then the filtrate was concentrated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (n-hexane/ethyl acetate=90/10→60/40) to obtain 37 mg of the title compound (yield: 27%) as an oil.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 4 days
  4. extractionfollowed by extraction with dichloromethane
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationThe desiccant was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by NH silica gel column chromatography (n-hexane/ethyl acetate=90/10→60/40)

Sources & evidence

ORD record
ord-759e2f976f5d4cf9a1f8d4bda0eebe71
Source dataset
uspto-grants-2015_12
Patent number
US09221811B2

Reaction notes

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