Dichloromethane → HCID 45377279, compound

HRID 1627224Notes

Reaction equation

HRID 1627224 reaction equation
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(OC([N:26]1[C:34]2[C:29](=[CH:30][C:31](Br)=[CH:32][CH:33]=2)[CH:28]=[C:27]1[C:36]1[CH:41]=[CH:40][C:39]([F:42])=[C:38]([CH3:43])[CH:37]=1)=O)(C)(C)C.C([O-])(=O)C.[K+].ClCCl.Br[C:53]1[N:57]([CH3:58])[N:56]=[C:55]([C:59]([NH:61][CH2:62][C:63]2[CH:71]=[CH:70][C:66]([C:67]([OH:69])=[O:68])=[CH:65][CH:64]=2)=[O:60])[CH:54]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CN(C)C=O.C(OCC)(=O)C>[F:42][C:39]1[CH:40]=[CH:41][C:36]([C:27]2[NH:26][C:34]3[C:29]([CH:28]=2)=[CH:30][C:31]([C:53]2[N:57]([CH3:58])[N:56]=[C:55]([C:59]([NH:61][CH2:62][C:63]4[CH:71]=[CH:70][C:66]([C:67]([OH:69])=[O:68])=[CH:65][CH:64]=4)=[O:60])[CH:54]=2)=[CH:32][CH:33]=3)=[CH:37][C:38]=1[CH3:43]

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 56850540HCID 56850540, compoundHCID 58506204HCID 58506204, compound

Product 1

HCID 45377279HCID 45377279, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of bis(pinacolato)diboron (94 mg,0.327 mmol), 5-Bromo-2-(4-fluoro-3-methyl-phenyl)-indole-1-carboxylic acid tert-butyl ester (75 mg, 0.18 mmol), and potassium acetate (55 mg, 55 mmol) in anhydrous 1,4-dioxane (250 uL) is added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (PdCl2(dppf)*CH2Cl2) (45 mg, 0.06 mmol). The reaction mixture is heated under reflux at 100° C. for 2 hours under nitrogen. Under nitrogen, 4-{[(5-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-amino]-methyl}-benzoic acid is added in N,N dimethylformamide (1 ml), followed by aqueous Na2CO3 (1 ml, 2N) and additional catalyst (20 mg). The reaction mixture is heated at 85° C. for 8 hours. The reaction mixture is diluted with 20 ml ethyl acetate, passed through a plug of celite and washed with water. The aqueous layer is evaporated, taken up in TFA/DCM (1:1, 5 ml) and stirred for 30 minutes. The solvent is evaporated in vacuo and the residue purified on reverse-phase HPLC to give the title compound 20 mg, (48%) LC/MS ESI m/z (M+H)+=484.5.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureThe reaction mixture is heated at 85° C. for 8 hours
  3. washwashed with water
  4. customThe aqueous layer is evaporated
  5. customThe solvent is evaporated in vacuo
  6. customthe residue purified on reverse-phase HPLC

Sources & evidence

ORD record
ord-400217dbb1f8477b8228b3413a9ac8c6
Source dataset
uspto-grants-2014_07
Patent number
US08785489B2

Reaction notes

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