Potassium Carbonate → HCID 178495679, compound

HRID 1751631Notes

Reaction equation

HRID 1751631 reaction equation
[CH3:1][CH:2]([CH3:36])[C@H:3]([NH:31][C:32](=[O:35])[O:33][CH3:34])[C:4](=[O:30])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)=[CH:13][N:14]=1.Br[C:38]1[CH:39]=[C:40]2[C:63](=[CH:64][CH:65]=1)[C:44]1[NH:45][C:46]([C@@H:48]3[CH2:52][C@H:51]([CH2:53][O:54][CH3:55])[CH2:50][N:49]3[C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])=[N:47][C:43]=1[CH:42]=[CH:41]2.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>[CH3:34][O:33][C:32]([NH:31][C@@H:3]([CH:2]([CH3:36])[CH3:1])[C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]([C:38]3[CH:39]=[C:40]4[C:63](=[CH:64][CH:65]=3)[C:44]3[NH:45][C:46]([C@@H:48]5[CH2:52][C@H:51]([CH2:53][O:54][CH3:55])[CH2:50][N:49]5[C:56]([O:58][C:59]([CH3:62])([CH3:60])[CH3:61])=[O:57])=[N:47][C:43]=3[CH:42]=[CH:41]4)=[CH:19][CH:20]=2)=[CH:13][N:14]=1)=[O:30])=[O:35]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57462153Methyl ((S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamateHCID 178495670HCID 178495670, compound

Product 1

HCID 178495679HCID 178495679, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl (S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (260 mg, 0.524 mmol), (2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (201 mg, 0.437 mmol), Pd(PPh3)4 (50 mg, 0.0437 mmol) and K2CO3 (2 M in H2O, 0.55 mL, 1.1 mmol) were combined in DME (4 mL). The reaction mixture was degassed with bubbling N2, then heated to 85° C. for 5 h. Upon completion, the reaction mixture was cooled to RT, diluted with 5 mL MeOH, filtered and concentrated. The crude residue was purified by silica column chromatography (0% to 45% MeOH/EtOAc) to afford (2S,4S)-tert-butyl 2-(7-(4-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (163 mg, 50%).

Workup

  1. customThe reaction mixture was degassed with bubbling N2
  2. temperatureUpon completion, the reaction mixture was cooled to RT
  3. additiondiluted with 5 mL MeOH
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by silica column chromatography (0% to 45% MeOH/EtOAc)

Sources & evidence

ORD record
ord-5a4b044ee79949ddba5098872ff53c70
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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