Sodium Carbonate → HCID 86727192, compound

HRID 579368Notes

Reaction equation

HRID 579368 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:13])[C:5](=[O:14])[C:4]=1B(O)O.Br[C:19]1[S:23][C:22]([N:24]([CH3:35])[CH:25]2[CH2:30][C:29]([CH3:32])([CH3:31])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)=[N:21][N:20]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:13])[C:5](=[O:14])[C:4]=1[C:19]1[S:23][C:22]([N:24]([CH3:35])[CH:25]2[CH2:30][C:29]([CH3:31])([CH3:32])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)=[N:21][N:20]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 867271295-Bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amineHCID 86727191HCID 86727191, compound

Product 1

HCID 86727192HCID 86727192, compoundYield 25.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed reaction mixture of (4-methoxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)boronic acid (500 mg, 2.15 mmol), 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (858 mg, 2.57 mmol), tetrakis(triphenylphosphine)palladium(0) (248 mg, 0.215 mmol) and Na2CO3 (682 mg, 6.44 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was heated via microwave irradiation at 100° C. for 1 h. After cooling to room temperature, the mixture was filtered through celite, washed with MeOH then the filtrate was concentrated. The residue was purified by silica gel chromatography (2%˜10% 2M NH3 in MeOH/DCM) to give 4-methoxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one (240 mg, MS: 442.1 [M+H+].) (4 mg, MS: 442.0 [M+H+], LCMS Rt=1.25 min (LCMS method D); 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.55 (s, 1H), 8.14 (dd, J=8.08, 1.52 Hz, 1H), 7.72-7.81 (m, 1H), 7.61-7.69 (m, 1H), 7.33-7.45 (m, 1H), 4.61 (br. s., 1H), 3.94 (s, 3H), 3.78 (s, 3H), 3.11 (s, 3H), 1.95 (d, J=12.13 Hz, 2H), 1.79 (br. s., 2H), 1.50 (s, 6H), 1.39 (br. s., 6H).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through celite
  3. washwashed with MeOH
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by silica gel chromatography (2%˜10% 2M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-ad3065c61d15412b87bcb12c126f1301
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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