Potassium Carbonate → HCID 178502326, compound

HRID 1751434Notes

Reaction equation

HRID 1751434 reaction equation
[CH3:1][CH:2]([CH3:38])[C@H:3]([NH:33][C:34](=[O:37])[O:35][CH3:36])[C:4](=[O:32])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:14][C:13]2[C:15]3[C:20]([CH:21]=[CH:22][C:12]=2[N:11]=1)=[CH:19][C:18](B1OC(C)(C)C(C)(C)O1)=[CH:17][CH:16]=3.Br[C:40]1[CH:41]=[C:42]2[C:64](=[CH:65][CH:66]=1)[C:46]1[NH:47][C:48]([C@@H:50]3[C@@H:55]4[CH2:56][C@@H:52]([CH2:53][CH2:54]4)[N:51]3[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[N:49][C:45]=1[CH:44]=[CH:43]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>[CH3:36][O:35][C:34]([NH:33][C@@H:3]([CH:2]([CH3:38])[CH3:1])[C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:14][C:13]2[C:15]3[C:20]([CH:21]=[CH:22][C:12]=2[N:11]=1)=[CH:19][C:18]([C:40]1[CH:41]=[C:42]2[C:64](=[CH:65][CH:66]=1)[C:46]1[NH:47][C:48]([C@@H:50]4[C@@H:55]5[CH2:56][C@@H:52]([CH2:53][CH2:54]5)[N:51]4[C:57]([O:59][C:60]([CH3:62])([CH3:63])[CH3:61])=[O:58])=[N:49][C:45]=1[CH:44]=[CH:43]2)=[CH:17][CH:16]=3)=[O:32])=[O:37]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 178452509HCID 178452509, compoundHCID 178502307HCID 178502307, compound

Product 1

HCID 178502326HCID 178502326, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Methyl (S)-3-methyl-1-oxo-1-((S)-2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (372 mg, 0.715 mmol), (1R,3S,4S)-tert-butyl 3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (317 mg, 0.715 mmol), Pd(PPh3)4 (83 mg, 0.0715 mmol) and K2CO3 (2M in H2O, 0.7 mL, 1.4 mmol) were suspended in DME (3.6 mL). The mixture was degassed for 13 min with bubbling N2, then heated to reflux. After 18 h, the reaction mixture was cooled to RT and 5 mL MeOH was added. EtOAc was added and the organics were washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc) to afford the title compound (196 mg, 36%).

Workup

  1. customThe mixture was degassed for 13 min with bubbling N2
  2. temperatureheated to reflux
  3. addition5 mL MeOH was added
  4. additionEtOAc was added
  5. washthe organics were washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc)

Sources & evidence

ORD record
ord-a2c776383775405898e654c3e292cef1
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…