Potassium Carbonate → HCID 71711240, compound

HRID 528539Notes

Reaction equation

HRID 528539 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([NH:25][C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+]>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>[N:31]1[CH:36]=[C:35]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=2[N:12]2[CH2:17][CH2:16][O:15][C:14]3[CH:18]=[C:19]([S:22]([NH:25][C:26]4[S:30][N:29]=[CH:28][N:27]=4)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]2=3)[CH:34]=[N:33][CH:32]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 71711761HCID 71711761, compound

Product 1

HCID 71711240HCID 71711240, compoundYield 40.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with INTERMEDIATE D (0.100 g, 0.192 mmol), pyrimidin-5-ylboronic acid (Small Molecules, Inc., Hoboken, N.J., 0.036 g, 0.288 mmol), tetrakis(triphenylphosphine)palladium(0) (0.022 g, 0.019 mmol), and K2CO3 (0.133 g, 0.959 mmol). The solids were diluted with dioxane (1.279 mL) and water (0.639 mL), and the reaction was heated under microwave irradiation at 100° C. for 30 minutes. The reaction mixture was diluted with water, and washed with ether (the ether layer was extracted once more with water). The combined aqueous layers were acidified with 1.0N HCl, and then washed with DCM (×2). The combined organics were dried using a phase separator and concentrated. After concentration, the material was purified by reverse-phase preparative HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min) to provide 4-(2-(pyrimidin-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.040 g, 0.077 mmol) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.45 (m, J=13.00 Hz, 1H) 3.76 (m, J=11.20 Hz, 1 H) 4.06-4.15 (m, 1 H) 4.31 (m, J=10.50 Hz, 1 H) 6.38 (d, J=8.22 Hz, 1 H) 6.98-7.00 (m, 1 H) 7.01-7.03 (m, 1 H) 7.73 (d, J=8.41 Hz, 1H) 7.94 (dd, J=8.56, 2.01 Hz, 1 H) 7.99 (m, J=1.70 Hz, 1 H) 8.26 (s, 1 H) 8.90 (s, 2 H) 9.07 (s, 1 H). m/z (ESI) 520.8 (M+H)+.

Workup

  1. washwashed with ether (the ether layer
  2. extractionwas extracted once more with water)
  3. washwashed with DCM (×2)
  4. customThe combined organics were dried
  5. concentrationconcentrated
  6. concentrationAfter concentration
  7. customthe material was purified by reverse-phase preparative HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min)

Sources & evidence

ORD record
ord-a6fb40d775d44737b420bd42d82cd85e
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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