Hydrochloric Acid → 5-[4-(1-Acetyl-azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one

HRID 554847Notes

Reaction equation

HRID 554847 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH:17]=[CH:16][C:15]4[N:18]=[C:19]([C:21]5[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1.C(N(CC)CC)C.[C:38](Cl)(=[O:40])[CH3:39].Cl>C(Cl)Cl>[C:38]([N:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH:17]=[CH:16][C:15]4[N:18]=[C:19]([C:21]5[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1)(=[O:40])[CH3:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 249907925-(4-(azetidin-3-yloxy)-3-methoxyphenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one

Product 1

HCID 249907955-[4-(1-Acetyl-azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (75 mg, 0.171 mmol) and triethylamine (52.5 μL, 0.376 mmol) in dry CH2Cl2 (700 μL). Chill to 0° C. and add acetylchloride (13.4 μL, 0.188 mmol). Allow to warm to room temperature overnight. Add 1 N HCl solution and extract with CH2Cl2 (3×5 mL). Combine the organic portions and wash with water (2×5 mL). Dry the organic layer with Na2SO4, filter, and concentrate in vacuo. Purify the resulting residue on HPLC with 5 μm 30×75 mm XBridge C18 column; eluent: 34% water (with 10 mM NH4HCO3 added to pH=10/acetonitrile (isocratic) to give 39 mg, (48%). ES/MS m/z (35Cl) 481.8 [M+1]+.

Workup

  1. temperatureAllow to warm to room temperature overnight
  2. extractionextract with CH2Cl2 (3×5 mL)
  3. washCombine the organic portions and wash with water (2×5 mL)
  4. dry with materialDry the organic layer with Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the resulting residue on HPLC with 5 μm 30×75 mm XBridge C18 column
  8. additioneluent: 34% water (with 10 mM NH4HCO3 added to pH=10/acetonitrile (isocratic)
  9. customto give 39 mg, (48%)

Sources & evidence

ORD record
ord-7573378fed8242f295f46197740de1b0
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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