Potassium Carbonate → HCID 178502349, compound

HRID 1751424Notes

Reaction equation

HRID 1751424 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17](=[O:30])[C@@H:18]([NH:25][C:26](=[O:29])[O:27][CH3:28])[CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[N:11][C:7]=1[CH2:6][CH2:5]2.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[C:44]3[C:49](=[CH:50][CH:51]=2)[CH:48]=[C:47]([C:52]2[NH:56][C:55]([C@@H:57]4[CH2:61][CH2:60][CH2:59][N:58]4[C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:54][CH:53]=2)[CH:46]=[CH:45]3)O1.C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:28][O:27][C:26]([NH:25][C@@H:18]([CH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[C:10]1[NH:9][C:8]2[C:31]3[C:4]([CH2:5][CH2:6][C:7]=2[N:11]=1)=[CH:3][C:2]([C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[CH:48]=[C:47]([C:52]1[NH:56][C:55]([C@@H:57]4[CH2:61][CH2:60][CH2:59][N:58]4[C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:54][CH:53]=1)[CH:46]=[CH:45]2)=[CH:33][CH:32]=3)=[O:30])=[O:29]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 584986761,1-Dimethylethyl (2S)-2-[5-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthalenyl]-1H-imidazol-2-yl]-1-pyrrolidinecarboxylateHCID 178502347HCID 178502347, compound

Product 1

HCID 178502349HCID 178502349, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl (S)-2-((S)-2-(7-bromo-4,5-dihydro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate (211 mg, 0.408 mmol), (S)-tert-butyl 2-(5-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (220 mg, 0.449 mmol), Pd(PPh3)4 (47 mg, 0.0408 mmol) and K2CO3 (2M in H2O, 0.45 mL, 0.9 mmol) were suspended in DME (4 mL). The reaction mixture was degassed for 10 min with N2 then heated to 85° C. After 17 h, it was cooled to RT, diluted with MeOH, filtered over a thiol SPE column and concentrated. The crude residue was purified by silica column chromatography (0% to 40% MeOH/EtOAc) to afford the title compound (130 mg, 40%).

Workup

  1. customThe reaction mixture was degassed for 10 min with N2
  2. temperatureit was cooled to RT
  3. additiondiluted with MeOH
  4. filtrationfiltered over a thiol SPE column
  5. concentrationconcentrated
  6. customThe crude residue was purified by silica column chromatography (0% to 40% MeOH/EtOAc)

Sources & evidence

ORD record
ord-0298525bd7f64d26855f9324bbdd4756
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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