Potassium Carbonate → HCID 178502335, compound

HRID 1751429Notes

Reaction equation

HRID 1751429 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:45]=[CH:44][C:43]([C:46]2[NH:50][C:49]([C@@H:51]3[C@@H:56]4[CH2:57][C@@H:53]([CH2:54][CH2:55]4)[N:52]3[C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[N:48][CH:47]=2)=[CH:42][CH:41]=1.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]=[CH:42][C:43]([C:46]2[NH:50][C:49]([C@@H:51]4[C@@H:56]5[CH2:57][C@@H:53]([CH2:54][CH2:55]5)[N:52]4[C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[N:48][CH:47]=2)=[CH:44][CH:45]=1)=[CH:17][CH:16]=3)=[O:32])=[O:37]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66831127(1R,3S,4S)-tert-butyl 3-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylateHCID 178502307HCID 178502307, compound

Product 1

HCID 178502335HCID 178502335, compoundYield 83%

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 (396 mg, 0.761 mmol), (1R,3S,4S)-tert-butyl 3-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (382 mg, 0.913 mmol), Pd(PPh3)4 (88 mg, 0.0761 mmol) and K2CO3 (2M in H2O, 0.95 mL, 1.9 mmol) were suspended in DME (4 mL). The reaction mixture was degassed with N2 for 6 min then heated to reflux. After 6.5 h, the reaction mixture was cooled to RT, diluted with MeOH, filtered over a thiol SPE column and concentrated. The crude residue was purified by column chromatography (0% to 30% MeOH/EtOAc) to afford the title compound (461 mg, 83%).

Workup

  1. customThe reaction mixture was degassed with N2 for 6 min
  2. temperaturethen heated to reflux
  3. additiondiluted with MeOH
  4. filtrationfiltered over a thiol SPE column
  5. concentrationconcentrated
  6. customThe crude residue was purified by column chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-2dadad93bb064acc9c856a034a3b9569
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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