Potassium Carbonate → HCID 178502339, compound

HRID 1751673Notes

Reaction equation

HRID 1751673 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)O1.Br[C:36]1[C:37]([F:65])=[C:38]2[C:62](=[CH:63][CH:64]=1)[C:42]1[NH:43][C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57](=[O:60])[O:58][CH3:59])[CH:53]([CH3:55])[CH3:54])=[N:45][C:41]=1[CH:40]=[CH:39]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.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]>[F:65][C:37]1[C:36]([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)=[CH:64][CH:63]=[C:62]2[C:38]=1[CH:39]=[CH:40][C:41]1[N:45]=[C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57]([O:58][CH3:59])=[O:60])[CH:53]([CH3:54])[CH3:55])[NH:43][C:42]=12

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 178451892HCID 178451892, compoundHCID 178502338HCID 178502338, compound

Product 1

HCID 178502339HCID 178502339, compoundYield 71.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

(S)-tert-butyl 2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (250 mg, 0.48 mmol) and methyl (S)-1-((S)-2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (200 mg, 0.4 mmol), Pd(PPh3)4 (46 mg, 0.04 mmol), Pd(dppf)2Cl2 (29 mg, 0.04 mmol), and K2CO3 (2M in H2O, 0.67 mL, 1.34 mmoL) were combined in DME (6 mL). The mixture was degassed with bubbling N2 for 10 min the heated to 85° C. for 16 h. After cooling, the reaction mixture was diluted with EtOAc, and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford (S)-tert-butyl 2-(6′-fluoro-2′-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (213 mg, 71%).

Workup

  1. customThe mixture was degassed with bubbling N2 for 10 min the
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. washwashed successively with saturated aqueous NaHCO3 and brine
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-98683e761a8e4a6cb4197c039ec3a6d8
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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