Potassium Carbonate → (2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751333Notes

Reaction equation

HRID 1751333 reaction equation
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]2[NH:15][C:16](C3C=CC(B4OC(C)(C)C(C)(C)O4)=CC=3)=[CH:17][N:18]=2)[CH2:3]1.Br[C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[CH:41]=[C:40]([C:45]1[NH:49][C:48]([C@@H:50]3[CH2:54][CH2:53][CH2:52][N:51]3[C:55](=[O:65])[C@@H:56]([NH:60][C:61](=[O:64])[O:62][CH3:63])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=1)[CH:39]=[CH:38]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>[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8])[C@H:4]([C:14]2[NH:15][C:16]([C:35]3[CH:36]=[CH:37][C:42]([C:35]4[CH:44]=[CH:43][C:42]5[C:37](=[CH:38][CH:39]=[C:40]([C:45]6[NH:49][C:48]([C@@H:50]7[CH2:54][CH2:53][CH2:52][N:51]7[C:55](=[O:65])[C@@H:56]([NH:60][C:61]([O:62][CH3:63])=[O:64])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=6)[CH:41]=5)[CH:36]=4)=[CH:43][CH:44]=3)=[CH:17][N:18]=2)[CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 59166440Tert-butyl (2S,4S)-4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl)-1H-imidazol-2-YL)pyrrolidine-1-carboxylateHCID 59610262HCID 59610262, compound

Product 1

HCID 69675612(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylateYield 21.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (200 mg, 0.44 mmol) and methyl (S)-1-((S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (219 mg, 0.44 mmol) were combined in DME (5 mL). Pd(PPh3)4 (51 mg, 0.0446 mmol) and K2CO3 (2M H2O, 0.73 mL, 1.45 mmol) were added, and the solution was degassed with N2 for 10 min. The solution was heated to 85° C. and stirred o/n. The following morning, the solution was cooled to rt. The solution was diluted with EtOAc, washed with sat. NaHCO3, brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography to yield product (36 mg).

Workup

  1. customthe solution was degassed with N2 for 10 min
  2. temperatureThe following morning, the solution was cooled to rt
  3. additionThe solution was diluted with EtOAc
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-11b5914623dd457983e0031cb75195db
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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