Sodium Carbonate → HCID 178491857, compound

HRID 1473703Notes

Reaction equation

HRID 1473703 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.Br[C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:27]([N:30](CC3C=CC(OC)=CC=3)[C:31]3[S:32][CH:33]=[CH:34][N:35]=3)(=[O:29])=[O:28])=[CH:24][CH:25]=2)[CH:20]=[N:19][C:18]=1[OH:45].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[OH:45][C:18]1[N:19]=[CH:20][C:21]2[C:26]([C:17]=1[C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:3]=1[O:2][CH3:1])=[CH:25][CH:24]=[C:23]([S:27]([NH:30][C:31]1[S:32][CH:33]=[CH:34][N:35]=1)(=[O:29])=[O:28])[CH:22]=2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 178490986HCID 178490986, compound

Product 1

HCID 178491857HCID 178491857, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1,1′-bis(diphenylphosphino)ferrocene-palladium(ii) dichloride dichloromethane adduct (28.2 mg, 0.035 mmol), 2-methoxy-4-(trifluoromethyl)phenylboronic acid (76 mg, 0.346 mmol), 4-bromo-3-hydroxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (175 mg, 0.346 mmol) and sodium carbonate (2M, 346 μl, 0.691 mmol) in Dioxane was heated to 100° C. in a microwave for 1 h. LC/MS showed mostly product, after cooling to rt, the crude material was purified by reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 20 min. The pure fractions were combined and concentrated in vacuo. The residue was dissolved in DCM (2 ml) and TFA (0.2 ml). The mixture was shaken at room temperature at 2 hr. LC-MS indicated product as the major species. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (4 g), eluting with a gradient of 0% to 100% EtOAc in hexane and then washed with pure methanol, to provide 3-hydroxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide as yellow solid. m/z (ESI) 482.0 [M+1].

Workup

  1. customthe crude material was purified by reverse-phase preparative HPLC
  2. customover 20 min
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DCM (2 ml)
  5. customThe crude material was absorbed onto a plug of silica gel
  6. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (4 g)
  7. washeluting with a gradient of 0% to 100% EtOAc in hexane
  8. washwashed with pure methanol

Sources & evidence

ORD record
ord-e574663ea52647638f3934356c70ef40
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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