Potassium Carbonate → 1-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(1-{2-[methyl(phenylmethyl)amino]ethyl}-1H-pyrazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

HRID 2366855Notes

Reaction equation

HRID 2366855 reaction equation
[CH3:1][CH:2]([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)[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br[C:38]1[CH:39]=[N:40][N:41]([CH2:43][CH2:44][N:45]([CH3:53])[CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:42]=1>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>[CH3:3][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:38]3[CH:39]=[N:40][N:41]([CH2:43][CH2:44][N:45]([CH3:53])[CH2:46][C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH:42]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:1]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 671951472-(4-bromo-1H-pyrazol-1-yl)-N-methyl-N-(phenylmethyl)ethanamineHCID 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]carbamate

Product 1

HCID 671949601-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(1-{2-[methyl(phenylmethyl)amino]ethyl}-1H-pyrazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-Methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (300 mg, 0.721 mmol, for a preparation see Intermediate 52), potassium carbonate (149 mg, 1.081 mmol) and 2-(4-bromo-1H-pyrazol-1-yl)-N-methyl-N-(phenylmethyl)ethanamine (317 mg, 1.078 mmol, for a preparation see Intermediate 53) were stirred in ethanol (3 mL) and toluene (3.00 mL). The mixture was degassed, tetrakis(triphenylphosphine)palladium(0) (41.6 mg, 0.036 mmol) added, the mixture degassed again and heated to reflux (90° C.) under nitrogen for 4.5 hours. The mixture was cooled to room temperature, loaded on to a 5 g SCX cartridge, eluted with MeOH (50 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 5% 2M methanolic ammonia in DCM. The product containing fractions were evaporated to a colourless gum (223 mg).

Workup

  1. customThe mixture was degassed
  2. customthe mixture degassed again
  3. temperatureheated
  4. temperatureThe mixture was cooled to room temperature
  5. washeluted with MeOH (50 ml), 2M methanolic ammonia (25 ml)
  6. customthe basic fractions evaporated to dryness
  7. washeluted with a gradient of 0 to 5% 2M methanolic ammonia in DCM
  8. additionThe product containing fractions
  9. customwere evaporated to a colourless gum (223 mg)

Sources & evidence

ORD record
ord-24015c9cdc8a4b199698be41af16583a
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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