Water → HCID 86660858, compound

HRID 1619686Notes

Reaction equation

HRID 1619686 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:15])=[O:14])=[CH:9][C:8]=2[C:22]#[N:23])=[C:4]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)[CH:3]=1.[C:32]([O:36][C:37]([NH:39][CH2:40][C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:22]([C:8]1[CH:9]=[C:10]([S:13]([NH:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)(=[O:15])=[O:14])[CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:24]=[CH:25][C:2]([C:45]2[CH:44]=[CH:43][CH:42]=[C:41]([CH2:40][NH:39][C:37](=[O:38])[O:36][C:32]([CH3:34])([CH3:33])[CH3:35])[CH:46]=2)=[CH:3][C:4]=1[C:26]1[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=1)#[N:23]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 36846863-(Aminomethyl)benzeneboronic acid, N-BOC protectedHCID 71720541HCID 71720541, compound

Product 1

HCID 86660858HCID 86660858, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a 5 mL microwave vial 4-[4-bromo-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzene sulfonamide (Patent WO 2010079443, 500 mg, 0.97 mmol) was dissolved in 1,4-dioxane (3 mL) under nitrogen. (3-{[(Tert-butoxycarbonyl)amino]methyl}phenyl)boronic acid (362 mg, 1.44 mmol), bis(triphenylphosphine) palladium (II) dichloride (68 mg, 0.1 mmol), sodium carbonate (204 mg, 1.92 mmol) and water (0.5 mL) were added and the reaction vessel sealed and heated to 120° C. for 45 minutes in the microwave. The reaction mixture was partitioned between ethyl acetate (20 mL) and 0.2M aqueous HCl (20 mL). The organic layer was separated, filtered then concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™, 12 g silica, 99:1 DCM:Acetic acid to 90:10:1 DCM:MeOH:Acetic acid gradient) to afford the title compound (380 mg, 61%) as a pale orange solid.

Workup

  1. customthe reaction vessel sealed
  2. customThe reaction mixture was partitioned between ethyl acetate (20 mL) and 0.2M aqueous HCl (20 mL)
  3. customThe organic layer was separated
  4. filtrationfiltered
  5. concentrationthen concentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ISCO™, 12 g silica, 99:1 DCM:Acetic acid to 90:10:1 DCM:MeOH:Acetic acid gradient)

Sources & evidence

ORD record
ord-dc9e2aeaf9a94f4fbdcef18520a3a030
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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