Sodium Carbonate → HCID 58827084, compound

HRID 1877931Notes

Reaction equation

HRID 1877931 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[CH2:12][CH2:11]1)[C:5]#[N:6].[CH3:18]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[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>[CH:17]1[N:16]=[CH:15][N:14]2[CH:10]([C:9]3[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[CH3:18])[CH2:11][CH2:12][C:13]=12

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 14797Potassium HydroxideHCID 574072TrimethylboroxineHCID 588270573-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

Product 1

HCID 58827084HCID 58827084, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 3-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (0.100 g, 0.347 mmol) given in Example 3 (table 2) and trimethylboroxine (0.145 g, 1.04 mmol) in DME (3 mL), aqueous solutions of Na2CO3 (0.69 mL, 2 M) and KOH (0.17 mL, 2 M) are added. After degassing with nitrogen, Pd(PPh3)4 (0.040 g, 0.035 mmol) is added. The mixture is heated in a microwave reactor at 130° C. 1.5 h. At that point LCMS showed consumption of the starting material. The solution is diluted with ethyl acetate and saturated sodium bicarbonate. The resulting aqueous layer is extracted further with ethyl acetate (3×). The combined organic layers are washed with brine and dried over anhydrous sodium sulfate. After concentration the crude product is filtered through 0.45 μm filter and then purified by preparative HPLC (0% for 5 minutes and 0-34% acetonitrile with 0.1% TFA in 17 minutes). MS (ESI) m/z 224.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.33-2.42 (m, 1 H), 2.43 (s, 3 H), 2.84-2:95 (m, 2 H), 3.07-3.18 (m, 1 H), 5.54 (dd, J=8.1, 4.8 Hz, 1 H), 6.65 (d, J=8.1 Hz, 1 H), 6.83 (s, 1 H), 7.32 (s, 1 H), 7.41 (d, J=8.1 Hz, 1 H), 7.50 (s, 1 H).

Workup

  1. additionare added
  2. additionis added
  3. custom1.5 h
  4. customconsumption of the starting material
  5. additionThe solution is diluted with ethyl acetate and saturated sodium bicarbonate
  6. extractionThe resulting aqueous layer is extracted further with ethyl acetate (3×)
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationAfter concentration the crude product
  10. filtrationis filtered through 0.45 μm
  11. filtrationfilter
  12. custompurified by preparative HPLC (0% for 5 minutes and 0-34% acetonitrile with 0.1% TFA in 17 minutes)

Sources & evidence

ORD record
ord-d33e09ee3a1a4b29926104a378a2a17d
Source dataset
uspto-grants-2012_11
Patent number
US08314097B2

Reaction notes

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