Hydrochloric Acid → HCID 68161788, compound

HRID 2041761Notes

Reaction equation

HRID 2041761 reaction equation
[ClH:1].Cl.[C:3]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[CH:13][CH:14]=2)[C@H:9]([NH2:22])[CH2:8][C@@H:7]1[CH3:23])(=[O:5])[CH3:4].CC(C)([O-])C.[Na+].Br[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][N:32]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.[Na].Cl>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOCC>[ClH:1].[C:3]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[CH:13][CH:14]=2)[C@H:9]([NH:22][C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][N:32]=2)[CH2:8][C@@H:7]1[CH3:23])(=[O:5])[CH3:4]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 5642162-Bromo-5-methylpyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2×HCID 5360545SodiumHCID 23676156Sodium t-butoxideHCID 68161466HCID 68161466, compound

Product 1

HCID 68161788HCID 68161788, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinamine di-hydrochloride (for a preparation see intermediate 61) (250 mg, 0.700 mmol), sodium tert-butoxide (336 mg, 3.50 mmol), 2-bromo-5-methylpyridine (132 mg, 0.770 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (55.0 mg, 0.140 mmol) and tris(dibenzylideneacetone)dipalladium(0) (64.1 mg, 0.070 mmol) was stirred in toluene (12 mL) at 75° C. under nitrogen for 5 h. An extra portion of sodium tert-butoxyde (81 mg, 0.84 mmol), Davephos (55.0 mg, 0.140 mmol) and tris(dibenzylideneacetone)dipalladium(0) (64.1 mg, 0.070 mmol) was added after having cooled the mixture down and the resulting mixture was stirred at 85° C. for 60 h under nitrogen, then cooled to room temperature and filtered through celite. The insoluble material was rinsed with DCM, stirred in 5% MeOH in DCM (100 mL) then filtered off. The combined filtrate and washings were concentrated in vacuo. Purification of the residue by flash chromatography on silica gel using a 20 G silica cartridge (gradient:0 to 3% MeOH in DCM) gave a residue which was dissolved in AcOEt. The resulting solution was treated with HCl (1.0M in Et2O, 3 mL) then concentrated in vacuo. Trituration of the residue with Et2O gave (cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-N-(5-methyl-2-pyridinyl)-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (143 mg, 0.347 mmol, 50%) as an off white solid.

Workup

  1. temperatureafter having cooled the mixture down
  2. temperaturecooled to room temperature
  3. filtrationfiltered through celite
  4. washThe insoluble material was rinsed with DCM
  5. stirringstirred in 5% MeOH in DCM (100 mL)
  6. filtrationthen filtered off
  7. concentrationThe combined filtrate and washings were concentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel using a 20 G silica cartridge (gradient:0 to 3% MeOH in DCM)
  9. customgave a residue which
  10. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-082d886e42774e7aad7d9b200432eac3
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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