Potassium Carbonate → HCID 178502301, compound

HRID 2172419Notes

Reaction equation

HRID 2172419 reaction equation
Br[C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12](=[O:22])[C@@H:13]([NH:17][C:18](=[O:21])[O:19][CH3:20])[CH:14]([CH3:16])[CH3:15])=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[C:35]3[CH2:37][O:38][C:39]4[CH:63]=[C:62]5[C:42]([CH:43]=[CH:44][C:45]6[N:49]=[C:48]([CH:50]7[CH2:54][CH2:53][CH2:52][N:51]7[C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[NH:47][C:46]=65)=[CH:41][C:40]=4[C:34]3=[CH:33][CH:32]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CN(C)C=O.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]>[CH3:20][O:19][C:18]([NH:17][C@H:13]([C:12]([N:8]1[CH2:9][CH2:10][CH2:11][CH:7]1[C:5]1[NH:6][C:2]([C:31]2[CH:36]=[C:35]3[CH2:37][O:38][C:39]4[CH:63]=[C:62]5[C:42]([CH:43]=[CH:44][C:45]6[N:49]=[C:48]([CH:50]7[CH2:54][CH2:53][CH2:52][N:51]7[C:55]([O:57][C:58]([CH3:59])([CH3:60])[CH3:61])=[O:56])[NH:47][C:46]=65)=[CH:41][C:40]=4[C:34]3=[CH:33][CH:32]=2)=[CH:3][N:4]=1)=[O:22])[CH:14]([CH3:16])[CH3:15])=[O:21]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateHCID 178451670HCID 178451670, compound

Product 1

HCID 178502301HCID 178502301, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (1.48 g, 3.97 mmol), tert-butyl 2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidine-1-carboxylate (1.88 g, 1.48 mmol), tetrakis(triphenyl phosphine)palladium(0) (191 mg, 0.16 mmol) and dichloro[1,1′-bis(diphenylphosphino) ferrocene]palladium(II) (242 mg, 0.33 mmol) in a mixture of 1,2-dimethoxyethane (37.0 mL) and dimethylformamide (6 mL) was added a solution of potassium carbonate (2M in water, 5 mL, 9.93 mmol). The resulting mixture was degassed and then heated to 85° C. under argon for 18 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to yield tert-butyl 2-[9-(2-{1-[N-(methoxycarbonyl)valyl]pyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidine-1-carboxylate (1.45 mg, 59%). LCMS-ESI+: calculated for C41H47N7O6 73 733.86; observed [M+1]+: 734.87.

Workup

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography

Sources & evidence

ORD record
ord-60300561c033428b99acef4a568fb7f7
Source dataset
uspto-grants-2015_06
Patent number
US09051340B2

Reaction notes

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