Hydrochloric Acid → 1-methylethyl((cis)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

HRID 2366925

Reaction equation

HRID 2366925 reaction equation
CC([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)C.[CH3:31][CH:32](OC(=O)NC1C2C(=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)N(C(=O)C)C(C)C1)[CH3:33].Br[C:62]1[CH:63]=[N:64][N:65]([CH2:67][CH2:68][N:69]([CH3:71])[CH3:70])[CH:66]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:78].CO>C(O)C.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:78].[CH3:31][CH:32]([N:6]([C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:62]3[CH:63]=[N:64][N:65]([CH2:67][CH2:68][N:69]([CH3:71])[CH3:70])[CH:66]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[C:5](=[O:30])[OH:4])[CH3:33]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 21859709[2-(4-Bromopyrazol-1-yl)ethyl]dimethylamineHCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 774200021-Methylethyl [1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Product 1

HCID 867623481-methylethyl((cis)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

1-Methylethyl[(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 12) (120 mg, 0.288 mmol), [2-(4-bromo-1H-pyrazol-1-yl)ethyl]dimethylamine (for a preparation see Intermediate 15) (85 mg, 0.390 mmol) and potassium carbonate (51.8 mg, 0.375 mmol) were stirred in ethanol (1.5 ml) and toluene (1.5 ml) and the mixture degassed. Tetrakis(triphenylphosphine)palladium(0) (16.65 mg, 0.014 mmol) was added, the mixture degassed again and heated to reflux (85° C.) overnight. The mixture was cooled to room temperature, partitioned between ethyl acetate (35 ml) and sat. sodium hydrogen carbonate:water (1:1, 10 ml). The aqueous layer was run off and the organic washed (sat. sodium hydrogen carbonate:water (1:1, 10 ml)), dried (magnesium sulfate) and evaporated to an orange residue. The residue was loaded on to a 12+M Biotage silica column and eluted with DCM:2M Methanolic ammonia (0 to 15%). The product containing fractions were evaporated to dryness then dissolved in MeOH (1 ml) and 1.25M HCl in MeOH (0.128 ml, 0.159 mmol) was added and the mixture evaporated to an off white solid (59 mg). LCMS (Method C): Rt=0.64, MH+=428

Workup

  1. customtoluene (1.5 ml) and the mixture degassed
  2. customthe mixture degassed again
  3. temperatureheated
  4. temperatureThe mixture was cooled to room temperature
  5. custompartitioned between ethyl acetate (35 ml) and sat. sodium hydrogen carbonate:water (1:1, 10 ml)
  6. washthe organic washed (sat. sodium hydrogen carbonate:water (1:1, 10 ml))
  7. dry with materialdried (magnesium sulfate)
  8. customevaporated to an orange residue
  9. washeluted with DCM
  10. additionThe product containing fractions
  11. customwere evaporated to dryness
  12. dissolutionthen dissolved in MeOH (1 ml)
  13. customthe mixture evaporated to an off white solid (59 mg)

Sources & evidence

ORD record
ord-97a800e0c9b3405d9622a642b1e21b99
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Linked notes

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