Toluene → HCID 68315261, compound

HRID 1618960Notes

Reaction equation

HRID 1618960 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3](B(O)O)[CH:2]=1.Cl[C:15]1[N:20]=[C:19]([C:21]2[NH:29][C:28]3[C:27]4([CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]4)[CH2:26][NH:25][C:24](=[O:41])[C:23]=3[CH:22]=2)[CH:18]=[CH:17][N:16]=1.C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>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.CCO>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:15]2[N:20]=[C:19]([C:21]3[NH:29][C:28]4[C:27]5([CH2:33][CH2:32][NH:31][CH2:30]5)[CH2:26][NH:25][C:24](=[O:41])[C:23]=4[CH:22]=3)[CH:18]=[CH:17][N:16]=2)[CH:2]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 2734663Quinoline-3-boronic acidHCID 86671416HCID 86671416, compound

Product 1

HCID 68315261HCID 68315261, compoundYield 47.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of quinolin-3-ylboronic acid (53.2 μmol, 9.2 mg), D7 (53.2 μmol, 21.5 mg), 2 N aqueous K2CO3 (106 μL), toluene (837 μL) and EtOH (209 μL) was purged with nitrogen. Then tetrakis(triphenylphosphine)palladium(0) (2.7 μmol; 3.1 mg) was added. The reaction mixture was stirred for 15 minutes at 140° C. in the microwave. The mixture was washed with water (1 mL). Brine (1 mL) was added to the aqueous phase, followed by an extraction with EtOAc (2×2 mL). The combined organic phase was concentrated. The residue was treated with 4N HCl in dioxane (2 mL) at room temperature for 30 minutes. The mixture was centrifuged and decanted. Subsequently, the residue was suspended in diethyl ether, centrifuged and decanted for another 2 times. The residue was dried in vacuo and purified by semi-preparative HPLC (method A), which obtained 10.1 mg of the desired product as a TFA salt (37%). 1H NMR (400 MHz, DMSO-D6, 300K): δ=2.21 (1H, m), 2.55 (1H, m), 3.50 (6H, m), 7.50 (1H, d, J=2.2 Hz), 7.56 (1H, br s), 7.73 (1H, m), 7.90 (1H, m), 7.91 (1H, d, J=5.4 Hz); 8.14 (1H, br d, J=8.6 Hz), 8.23 (1H, br d, J=8.2 Hz), 8.90 (1H, d, J=5.4 Hz), 9.10 (1H, br s), 9.25 (1H, br s), 9.49 (1H, d, J=2.1 Hz), 10.08 (1H, d, 2.1 Hz), 12.02 (1H, br s); MS (ES) C23H20N6O requires: 396. found: 397.3 [M+H]+.

Workup

  1. customwas purged with nitrogen
  2. washThe mixture was washed with water (1 mL)
  3. additionBrine (1 mL) was added to the aqueous phase
  4. extractionfollowed by an extraction with EtOAc (2×2 mL)
  5. concentrationThe combined organic phase was concentrated
  6. additionThe residue was treated with 4N HCl in dioxane (2 mL) at room temperature for 30 minutes
  7. customdecanted
  8. customdecanted for another 2 times
  9. customThe residue was dried in vacuo
  10. custompurified by semi-preparative HPLC (method A), which

Sources & evidence

ORD record
ord-d33c2fe7b06e4ab2b3a88d4cf89ee5af
Source dataset
uspto-grants-2014_07
Patent number
US08772286B2

Reaction notes

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