Potassium Carbonate → HCID 86683590, compound

HRID 1509174Notes

Reaction equation

HRID 1509174 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:44][C:45]1[N:46]=[CH:47][S:48][CH:49]=1>CN(C)C=O.C(=O)(O)[O-].[Na+]>[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][C:4]=2[N:3]1[CH2:44][C:45]1[N:46]=[CH:47][S:48][CH:49]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27632894-(Chloromethyl)-1,3-thiazole hydrochlorideHCID 67256382HCID 67256382, compound

Product 1

HCID 86683590HCID 86683590, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

In a 15 mL reaction tube was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (50 mg, 0.106 mmol), potassium carbonate (59 mg, 0.424 mmol) and 4-(chloromethyl)thiazole HCl salt (54 mg, 0.318 mmol) in anhydrous N,N-dimethylformamide (1 mL) to give an orange suspension. The reaction mixture was stirred at 80° C. for one hour. The reaction mixture was allowed to cool to room temperature, diluted with saturated sodium bicarbonate solution (5 mL) and extracted into dichloromethane (3×3 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a yellow oil. This was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 0:100) to give the desired product as an off-white solid (54 mg, 90% yield). 1H-NMR (500 MHz, CDCl3) δ 8.70 (1H, s), 7.61 (1H, s), 7.28 (1H, s), 7.12-7.27 (7H, m), 7.03-7.12 (2H, m), 5.23 (2H, s), 4.99 (1H, br s), 4.86 (2H, s), 2.10-2.60 (4H, m), 2.41-2.06 (1H, m), 1.65-1.79 (1H, m), 1.00-1.45 (9H, br m). LCMS (Method A) RT=7.11 min, M+H+=569.14.

Workup

  1. customIn a 15 mL reaction tube
  2. customto give an orange suspension
  3. temperatureto cool to room temperature
  4. extractionextracted into dichloromethane (3×3 mL)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customto give a yellow oil
  9. customThis was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 0:100)

Sources & evidence

ORD record
ord-277f4476fa2c403abf33a008ecc5c9ce
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…