Hydrochloric Acid → 1-Methylethyl {(cis)-1-acetyl-6-[6-(dimethylamino)-3-pyridinyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate hydrochloride

HRID 2366924Notes

Reaction equation

HRID 2366924 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].C(=O)([O-])[O-].[K+].[K+].O.[CH3:30][N:31]([CH3:41])[C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.[ClH:42]>C(O)C.C1(C)C=CC=CC=1.CO.CCOCC.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>[ClH:42].[C:18]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:35]3[CH:36]=[N:37][C:32]([N:31]([CH3:41])[CH3:30])=[CH:33][CH:34]=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

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 441190932-(Dimethylamino)pyridine-5-boronic acid hydrateHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 866692691-Methylethyl {(cis)-1-acetyl-6-[6-(dimethylamino)-3-pyridinyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate hydrochloride

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

In a carousel tube, 1-methylethyl[(cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Example 61) (80 mg, 0.217 mmol), potassium carbonate (59.9 mg, 0.433 mmol), tetrakis(triphenylphosphine)palladium(0) (12.52 mg, 10.83 μmol) and [6-(dimethylamino)-3-pyridinyl]boronic acid hydrate (47.8 mg, 0.26 mmol, available from Apollo) were dissolved in Ethanol (0.5 mL) and Toluene (0.5 mL). The tube was placed in a carousel and heated under nitrogen for 18 hr at 90° C. The reaction mixture was filtered and the solvent evaporated before being taken up in DCM and purified by SP4 on a 12+M silica cartridge using a gradient of 20-100% EtOAc in cyclohexane. Appropriate fractions were collected and concentrated. The sample was dissolved in 1:1 MeOH:DMSO 1 mL and purified by MDAP. The solvent was evaporated in vacuo. To form a salt, the product was dissolved in MeOH and HCl (0.217 mL, 0.217 mmol) 1M in ether was added. Solvent was evaporated to yield the product as a pale yellow solid (76 mg). LCMS (Method C): Rt=0.66, MH+=411

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent evaporated
  3. custompurified by SP4 on a 12+M silica cartridge
  4. customAppropriate fractions were collected
  5. concentrationconcentrated
  6. dissolutionThe sample was dissolved in 1:1 MeOH
  7. customDMSO 1 mL and purified by MDAP
  8. customThe solvent was evaporated in vacuo
  9. customTo form a salt
  10. customSolvent was evaporated

Sources & evidence

ORD record
ord-59e1c1afe29d4571abd72b8d6f387631
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…