Dichloromethane → HCID 178468577, compound

HRID 2068282Notes

Reaction equation

HRID 2068282 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](COCC[Si](C)(C)C)[N:6]=[C:5]2[NH:19][C:20]1[N:24]([C@H:25]2[CH2:30][CH2:29][C@H:28]([O:31][Si](C(C)(C)C)(C)C)[CH2:27][CH2:26]2)[C:23]2[CH:39]=[CH:40][C:41]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:42][C:22]=2[N:21]=1.O1[CH2:53][CH2:52][O:51][CH2:50]C1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:31][C@H:28]1[CH2:29][CH2:30][C@H:25]([N:24]2[C:23]3[CH:39]=[CH:40][C:41]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:42][C:22]=3[N:21]=[C:20]2[NH:19][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:4]4[CH:5]=[N:19][CH:20]=[CH:53][C:52]=4[O:51][CH3:50])[CH:3]=3)[NH:7][N:6]=2)[CH2:26][CH2:27]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 178468576HCID 178468576, compound

Product 1

HCID 178468577HCID 178468577, compoundYield 178.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-(trans-4-(tert-butyldimethylsilyloxy)cyclohexyl)-1H-benzo[d]imidazole-5-carboxylate (90.1 mg, 0.000121 mol) and 4-methoxypyridin-3-yl-3-boronic acid (22 mg, 0.00014 mol) were added to a 20 mL vial and dissolved in 1,4-dioxane (2 mL, 0.02 mol). To the reaction mixture was added 2 M sodium carbonate in water (0.3 mL) followed by the addition of [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complexed with dichloromethane (1:1) (10 mg, 0.00001 mol). The reaction mixture was heated under nitrogen at 90° C. for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by combiflash chromatography using methanol/methylene chloride as eluent and a 40 g silica gel cartridge. A gradient was run from 0% methanol to 4% methanol over 20 minutes. Concentrating the product fractions under high vacuum gave 56.8 mg of the title compound as a foam.

Workup

  1. washwashed with saturated sodium bicarbonate solution and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by combiflash chromatography
  5. concentrationConcentrating the product fractions under high vacuum

Sources & evidence

ORD record
ord-ab4b9f2e920f4709a4840ee90269579e
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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