1,2-Dimethoxyethane → HCID 67189214, compound

HRID 885996Notes

Reaction equation

HRID 885996 reaction equation
Br[C:2]1[C:3]([O:24][CH3:25])=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[C:14](=[O:22])[NH:15][C:16]([CH3:21])([CH3:20])[CH2:17][C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.Cl.[N:27]1([CH2:33][C:34]2[CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:37]=[CH:38][CH:39]=2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.P([O-])([O-])([O-])=O.[K+].[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.O>[CH3:20][C:16]1([CH3:21])[NH:15][C:14](=[O:22])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([C:36]5[CH:37]=[CH:38][CH:39]=[C:34]([CH2:33][N:27]6[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]6)[CH:35]=5)[C:3]([O:24][CH3:25])=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 46739016HCID 46739016, compoundHCID 67188040HCID 67188040, compound

Product 1

HCID 67189214HCID 67189214, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of Example 490 (0.05 g, 0.118 mmol), 3-(piperidin-1-ylmethyl)-phenylboronic acid pinacol ester hydrochloride (0.0478 g, 0.141 mmol), potassium phosphate (0.1 g, 0.471 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0082 g, 0.0071 mmol) was degassed under 3 cycles of nitrogen and vacuum. DME (1.2 mL) and water (0.3 ml) were added and the mixture was degassed as before. The mixture was heated to 120° C. under microwave irradiation in a sealed tube for 1 h. Water (15 mL) and DCM (15 mL) were added. The aqueous fraction was separated and extracted with DCM (2×10 mL). The combined organic fractions were filtered through a Whatman 1μ PTFE tube and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (0.0243 g, 40%) as a colourless solid. δH (CDCl3) 7.76 (1H, s), 7.45 (1H, s), 7.41-7.31 (2H, m), 7.30-7.25 (1H, m), 6.57 (1H, s), 5.28 (1H, s), 4.37-4.32 (2H, m), 4.21-4.16 (2H, m), 3.78 (3H, s), 3.54 (2H, s), 2.84 (2H, s), 2.49-2.37 (4H, m), 1.64-1.54 (4H, m), 1.48-1.35 (8H, m). LCMS (ES+) 519.3 (M+H)+, RT 2.32 minutes (Method 1).

Workup

  1. customthe mixture was degassed as before
  2. additionWater (15 mL) and DCM (15 mL) were added
  3. customThe aqueous fraction was separated
  4. extractionextracted with DCM (2×10 mL)
  5. filtrationThe combined organic fractions were filtered through a Whatman 1μ PTFE tube
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-622dbc25561f4ecab65ca5a1fef26e0a
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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