Sodium Bicarbonate → (S)-tert-butyl 2-(5-(4'-(2-acetamido-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 20886Notes

Reaction equation

HRID 20886 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([NH:13][C:14](=[O:16])[CH3:15])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[NH:35][C:34]([C@@H:36]4[CH2:40][CH2:39][CH2:38][N:37]4[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[N:33][CH:32]=3)=[CH:27][CH:26]=2)O1.C([O-])(O)=O.[Na+]>COCCOC.O.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>[C:14]([NH:13][C:11]1[NH:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:25]3[CH:26]=[CH:27][C:28]([C:31]4[NH:35][C:34]([C@@H:36]5[CH2:40][CH2:39][CH2:38][N:37]5[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[N:33][CH:32]=4)=[CH:29][CH:30]=3)=[CH:3][CH:4]=2)=[CH:9][N:10]=1)(=[O:16])[CH3:15]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 10468856N-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-acetamideHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 66820312(S)-tert-butyl 2-(5-(4'-(2-acetamido-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of N-(5-(4-bromophenyl)-1H-imidazol-2-yl)acetamide (0.604 g, 2.16 mmol), (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (0.950 g, 2.16 mmol), NaHCO3 (0.636 g, 7.57 mmol) in DME (20 mL) and H2O (5 mL) was degassed by evacuating and back-filling with N2 (×3). To this solution Pd(PPh3)4 (0.125 g, 0.11 mmol) was added and the suspension heated at 125° C. for 24 h. The mixture was evaporated to dryness in vacuo and the residue was purified by column chromatography (Biotage) eluting with a gradient of 0 to 10% MeOH in CH2C2. The material was then purified by prep HPLC (CH3CN—H2O—NH4OAc) to afford the title compound as a colorless solid. 7.76 (app dd, J=8.4, 2.2 Hz, 4H), 7.69 (app d, J=8.4 Hz, 2H), 7.66 (app d, J=8.4 Hz, 2H), 7.45 (s, 1H), 7.23 (s, 1H), 3.66-3.72 (m, 1H), 3.48-3.53 (s, 1H), 2.34-2.46 (m, 1H), 2.18 (s, 3H), 1.96-2.10 (m, 3H), 1.46, 1.25 (s, 9H, rotamers, 1:2 ratio). LCMS: Anal. Calcd. for C29H32N6O3: 512; found: 513, 282 (M+H)+.

Workup

  1. customwas degassed
  2. customby evacuating and back-filling with N2 (×3)
  3. customThe mixture was evaporated to dryness in vacuo
  4. customthe residue was purified by column chromatography (Biotage)
  5. washeluting with a gradient of 0 to 10% MeOH in CH2C2
  6. customThe material was then purified by prep HPLC (CH3CN—H2O—NH4OAc)

Sources & evidence

ORD record
ord-12f547d012c34edfbb473b0f3007f583
Source dataset
uspto-grants-2010_06
Patent number
US07745636B2

Reaction notes

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