Sodium Carbonate → HCID 178502467, compound

HRID 1504310Notes

Reaction equation

HRID 1504310 reaction equation
[CH3:1][O:2][C:3](=[O:29])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([OH:16])[CH2:13][C@H:12]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25](Br)=[CH:24][CH:23]=2)[N:21]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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]>[CH3:1][O:2][C:3](=[O:29])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([OH:16])[CH2:13][C@H:12]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:38]3[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=3)=[CH:24][CH:23]=2)[N:21]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 178502465HCID 178502465, compound

Product 1

HCID 178502467HCID 178502467, compoundYield 78.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ((S)-1-{(2S,4S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-4-hydroxy-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.8 g, 3.87 mmol) in dioxane (30 mL) and water (10 mL), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (848 mg, 3.87 mmol), sodium carbonate (820 mg, 7.74 mmol) and Pd(dppf)Cl2 (316 mg, 0.39 mmol) were added and the reaction mixture was heated at reflux for 3 h, cooled to RT, filtered and concentrated, extracted with EtOAc (50 mL), and washed with water (50 mL). The organic layer was dried over sodium sulfate, filtered, concentrated and purified by silica gel column chromatography (eluted with 1% to 3% methanol in DCM) to give the title intermediate (1.45 g, 65% yield). 1H NMR (CH3OD, 400) δ (ppm) 7.70 (m, 2H), 7.67 (m, 2H), 7.45 (m, 2H), 7.29 (s, 1H), 6.80 (d, J=6.8 Hz, 1H), 5.82 (d, J=9.2 Hz, 1H), 5.29 (d, J=8.8 Hz, 1H), 4.59 (s, 1H), 4.34 (d, J=8.8 Hz, 1H), 4.16 (d, J=8.0 Hz, 1H), 3.95-4.04 (m, 1H), 3.79-3.83 (m, 1H), 3.76 (s, 3H), 2.55-2.69 (m, 1H), 2.32 (m, 1H), 1.60-2.03 (m, 1H), 1.00 (m, 3H), 0.3-0.85 (m, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. filtrationfiltered
  4. concentrationconcentrated
  5. extractionextracted with EtOAc (50 mL)
  6. washwashed with water (50 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography (eluted with 1% to 3% methanol in DCM)

Sources & evidence

ORD record
ord-6e9bb3d0516845289bae55c1562ca26a
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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