Ethanol → HCID 86669226, compound

HRID 2366827Notes

Reaction equation

HRID 2366827 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH:15][CH:16]=[O:17])[CH2:6][C@@H:5]1[CH2:18][CH3:19])(=[O:3])[CH3:2].[N:20]1([CH2:26][C:27]2[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>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.C1(C)C=CC=CC=1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:30]3[CH:29]=[CH:28][C:27]([CH2:26][N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[CH:32][CH:31]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:15][CH:16]=[O:17])[CH2:6][C@@H:5]1[CH2:18][CH3:19])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 23005343HCID 23005343, compound2×HCID 86669227HCID 86669227, compound

Product 1

HCID 86669226HCID 86669226, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

((cis)-1-acetyl-6-bromo-2-ethyl-1,2,3,4-tetrahydro-4-quinolinyl)formamide (for a preparation see Intermediate 44) (1 g, 3.08 mmol) and [4-(1-piperidinylmethyl)phenyl]boronic acid (1.572 g, 6.15 mmol, Intermediate 1) were mixed with Ethanol (8 mL), Toluene (8.00 mL). potassium carbonate (1.402 g, 10.15 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.355 g, 0.308 mmol) were added and the mixture was stirred under nitrogen, at reflux at 110° C. After 3 hours, another sample of tetrakis(triphenylphosphine)palladium(0) (0.355 g, 0.308 mmol) was added and the reaction was left to stir overnight. The reaction was evaporated to dryness. The residue was diluted with DCM (150 mL), washed (water (150 mL), sat. sodium bicarbonate (200 mL), brine (200 mL)), dried (sodium sulfate), filtered and evaporated to dryness to give a black solid which was loaded onto an 20 g SCX-column, eluting with MeOH (120 mL) followed by MeOH/NH3 (300 mL). Product-containing fractions were evaporated to dryness to give a dark red solid which was purified on a 40+S Biotage silica column, eluting with DCM:2M MeOH/NH3 (1:0 to 19:1). Product-containing fractions were evaporated to dryness to give a yellow/orange solid (1.00 g).

Workup

  1. waitthe reaction was left
  2. stirringto stir overnight
  3. customThe reaction was evaporated to dryness
  4. additionThe residue was diluted with DCM (150 mL)
  5. washwashed (water (150 mL), sat. sodium bicarbonate (200 mL), brine (200 mL))
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto give a black solid which
  10. washeluting with MeOH (120 mL)
  11. customProduct-containing fractions were evaporated to dryness
  12. customto give a dark red solid which
  13. customwas purified on a 40+S Biotage silica column
  14. washeluting with DCM
  15. customProduct-containing fractions were evaporated to dryness

Sources & evidence

ORD record
ord-4a23717a725f4a56a8618b3b2f9ea9fd
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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