Potassium Carbonate → HCID 52935018, compound

HRID 2366906Notes

Reaction equation

HRID 2366906 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].Cl.[N:24]1([CH2:30][C:31]2[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C(N1C2C(=CC(C#C[Si](C)(C)C)=CC=2)[C@H](NC(=O)OC(C)(C)C)C[C@@H]1C)(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C.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>[C:18]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:34]3[CH:33]=[CH:32][C:31]([CH2:30][N:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:36][CH:35]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:22])[O:4][CH:2]([CH3:3])[CH3:1])[CH2:8][C@@H:9]1[CH3:21])(=[O:20])[CH3:19]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamateHCID 56773619HCID 56773619, compoundHCID 68184857HCID 68184857, compound

Product 1

HCID 52935018HCID 52935018, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1-Methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Example 4) (50 mg, 0.135 mmol), [4-(1-piperidinylmethyl)phenyl]boronic acid hydrochloride (for a preparation see Intermediate 1) (45.0 mg, 0.176 mmol), potassium carbonate (43.0 mg, 0.311 mmol) and tetrakis(triphenylphosphine)palladium(0) (7.82 mg, 6.77 μmol) were suspended in a mixture of Ethanol (0.5 ml) and Toluene (0.5 ml) and heated under microwave conditions in an Emrys Optimiser at 100° C. for 3 hours. Further tetrakis(triphenylphosphine)palladium(0) (7.82 mg, 6.77 μmol) added and the mixture heated at 90° C. thermally for 23 hours. The mixture was cooled to room temperature, loaded on to a 2 g SCX cartridge, eluted with MeOH (25 ml), 2M methanolic ammonia (25 ml) and the basic fractions evaporated to dryness. The residue was loaded on to a 12+M Biotage silica column and eluted with a gradient of 0 to 4% methanloic ammonia in DCM. The clean, product containing fractions were evaporated to a white solid (10 mg).

Workup

  1. temperaturethe mixture heated at 90° C. thermally for 23 hours
  2. temperatureThe mixture was cooled to room temperature
  3. washeluted with MeOH (25 ml), 2M methanolic ammonia (25 ml)
  4. customthe basic fractions evaporated to dryness
  5. washeluted with a gradient of 0 to 4% methanloic ammonia in DCM
  6. additionThe clean, product containing fractions
  7. customwere evaporated to a white solid (10 mg)

Sources & evidence

ORD record
ord-58417c117e7b4fb18a669aefef942490
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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