Sodium Carbonate → HCID 136340996, compound

HRID 1627232Notes

Reaction equation

HRID 1627232 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][C:9]([C:11]2[N:12](COCC[Si](C)(C)C)[C:13](Br)=[C:14]([Br:16])[N:15]=2)=[O:10])=[CH:3][CH:2]=1.C(OC([N:33]1[C:41]2[C:36](=[CH:37][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:39][CH:40]=2)[CH:35]=[C:34]1[C:51]1[O:55][N:54]=[C:53]([CH3:56])[N:52]=1)=O)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:1]1[CH:2]=[CH:3][C:4]([CH2:7][NH:8][C:9]([C:11]2[NH:15][C:14]([Br:16])=[C:13]([C:38]3[CH:37]=[C:36]4[C:41](=[CH:40][CH:39]=3)[NH:33][C:34]([C:51]3[O:55][N:54]=[C:53]([CH3:56])[N:52]=3)=[CH:35]4)[N:12]=2)=[O:10])=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58506151HCID 58506151, compoundHCID 66989360HCID 66989360, compound

Product 1

HCID 136340996HCID 136340996, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 4,5-dibromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid(pyridin-4-ylmethyl)-amide (280 mg, 0.57 mmol) and 2-(3-methyl-1,2,4-oxadiazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-indole-1-carboxylic acid tert-butyl ester (243 mg, 0.57 mmol) in toluene (5.0 ml) is added aqueous Na2CO3 solution (2M, 0.63 ml, 1.26 mmol). The mixture is purged with argon for 10 minutes. (Bis(di-t-butyl(4-dimethylaminutesophenyephosphine)dichloropalladium(II) (81 mg, 0.11 mmol) is added and the reaction mixture is sealed in a sealed tube and heated to 120° C. for 14 hours. The reaction mixture is diluted with ethyl acetate (25 ml), washed with water (15 ml), brine (15 ml), dried over MgSO4, filtered, and concentrated in vacuo. The crude material is purified on reversed phase HPLC. The resulting protected analog is dissolved in 50% trifluoroacetic acid in dichloromethane (10 ml). After 2 hours the solvent is evaporated in vacuo, and the product is purified by reverse phase HPLC, 25 mg, 9%, LC/MS ESI m/z (M+H)+=480.33.

Workup

  1. customThe mixture is purged with argon for 10 minutes
  2. customthe reaction mixture is sealed in a sealed tube
  3. washwashed with water (15 ml), brine (15 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material is purified on reversed phase HPLC
  8. dissolutionis dissolved in 50% trifluoroacetic acid in dichloromethane (10 ml)
  9. customAfter 2 hours the solvent is evaporated in vacuo
  10. customthe product is purified by reverse phase HPLC, 25 mg, 9%, LC/MS ESI m/z (M+H)+=480.33

Sources & evidence

ORD record
ord-352639ac86954d269f6e8f84f9775829
Source dataset
uspto-grants-2014_07
Patent number
US08785489B2

Reaction notes

Loading…