Potassium Carbonate → HCID 123139090, compound

HRID 1509201Notes

Reaction equation

HRID 1509201 reaction equation
[NH2:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[C:4]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:3]=1.Cl[CH2:34][S:35](Cl)(=[O:37])=[O:36].C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1>[C:22]([O:21][C:20](=[O:26])[NH:19][C:15]1([C:12]2[CH:11]=[CH:10][C:9]([C:5]3[C:4]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:3][C:2]4[NH:1][S:35](=[O:37])(=[O:36])[CH2:34][O:8][C:7]=4[N:6]=3)=[CH:14][CH:13]=2)[CH2:18][CH2:17][CH2:16]1)([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 77054(Chloromethyl)sulfonyl chlorideHCID 67257668HCID 67257668, compound

Product 1

HCID 123139090HCID 123139090, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a 40 mL reaction tube was added tert-butyl 1-(4-(5-amino-6-oxo-3-phenyl-1,6-dihydropyridin-2-yl)phenyl)cyclobutylcarbamate (500 mg, 1.159 mmol) in anhydrous pyridine (5 mL) to give a yellow solution. After stirring at room temperature for 15 minutes, chloromethanesulfonyl chloride (126 μl, 1.390 mmol) was added and the resulting solution stirred at room temperature for 3 hours. The reaction mixture was concentrated to dryness under reduced pressure and redissolved in anhydrous methanol (5 mL), followed by the addition of potassium carbonate (641 mg, 4.63 mmol) and heating to 60° C. overnight. The reaction mixture was allowed to cool to room temperature and concentrated to dryness under reduced pressure. The residue was redissolved in ethyl acetate (5 mL) and washed with 50:50 water:brine (2×5 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a brown oil. This was purified by Biotage chromatography (cyclohexane:ethyl acetate:dichloromethane:methanol, gradient elution from 80:10:10:0 to 0:90:10:0 then to 0:90:10) to give the desired product as an off-white solid (330 mg, 56% yield). 1H-NMR (500 MHz, d6-Acetone) δ 7.35 (1H, s), 7.23-7.32 (7H, m), 7.16-7.32 (2H, m), 5.39 (2H, s), 2.30-2.60 (4H, m), 2.00-2.12 (1H, m), 1.75-1.88 (1H, m), 1.05-1.40 (9H, br m). LCMS (Method A) RT=6.68 min, M+H+=508.01.

Workup

  1. customIn a 40 mL reaction tube
  2. customto give a yellow solution
  3. stirringthe resulting solution stirred at room temperature for 3 hours
  4. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  5. dissolutionredissolved in anhydrous methanol (5 mL)
  6. temperatureheating to 60° C. overnight
  7. temperatureto cool to room temperature
  8. concentrationconcentrated to dryness under reduced pressure
  9. dissolutionThe residue was redissolved in ethyl acetate (5 mL)
  10. washwashed with 50:50 water
  11. dry with materialbrine (2×5 mL), dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure
  14. customto give a brown oil
  15. customThis was purified by Biotage chromatography (cyclohexane
  16. washethyl acetate:dichloromethane:methanol, gradient elution from 80:10:10:0 to 0:90:10:0

Sources & evidence

ORD record
ord-3e8268da4a3f47458aceeee96969ace1
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…