Potassium Phosphate, Tribasic → HCID 86702341, compound

HRID 1524253Notes

Reaction equation

HRID 1524253 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][C@H:15]([CH3:18])[N:14]3[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:26][O:27][CH2:28][C@@H:29]1[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:31]([C:41]2[NH:42][C:43]([C:46]3[CH:51]=[CH:50][C:49](B4OC(C)(C)C(C)(C)O4)=[CH:48][CH:47]=3)=[CH:44][N:45]=2)[CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:22]([O:21][C:19]([N:14]1[C@@H:15]([CH3:18])[CH2:16][CH2:17][C@H:13]1[C:11]1[NH:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:49]3[CH:48]=[CH:47][C:46]([C:43]4[NH:42][C:41]([C@@H:31]5[CH2:30][C@H:29]([CH2:28][O:27][CH3:26])[CH2:33][N:32]5[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[N:45][CH:44]=4)=[CH:51][CH:50]=3)=[CH:3][CH:4]=2)=[CH:9][N:10]=1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 58209599HCID 58209599, compoundHCID 67682602HCID 67682602, compound

Product 1

HCID 86702341HCID 86702341, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (2S,5S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (1.0 g, 2.5 mmol) and (2S,4S)-tert-butyl 4-(methoxymethyl)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.4 g, 2.8 mmol) in DME (12.5 mL) was added tetrakis(triphenylphosphine)-palladium (0.28 g, 0.24 mmol) and aqueous potassium phosphate (2M, 3.7 mL, 7.4 mmol). The resulting slurry was degassed with argon for 5 min and heated to 80° C. for 18 h. The reaction was cooled to room temperature and diluted with a mixture of CH2Cl2 (10% MeOH). The solution was washed with water and brine. The aqueous layer was backextracted with CH2Cl2 (10% MeOH). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude oil was purified by column chromatography (SiO2, 50 to 100% EtOAc (5% MeOH)/Hexanes) to provide (2S,4S)-tert-butyl 2-(5-(4′-(2-((2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (1.2 g, 73%). LCMS-ESI+: calc'd for C39H50N6O5: 688.38 (M+). Found: 683.51 (M+H+).

Workup

  1. customThe resulting slurry was degassed with argon for 5 min
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with a mixture of CH2Cl2 (10% MeOH)
  4. washThe solution was washed with water and brine
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude oil was purified by column chromatography (SiO2, 50 to 100% EtOAc (5% MeOH)/Hexanes)

Sources & evidence

ORD record
ord-88c5236ed3ff4e04a927891f5d74cec6
Source dataset
uspto-grants-2015_07
Patent number
US09079887B2

Reaction notes

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