Water → HCID 68162631, compound

HRID 2041697Notes

Reaction equation

HRID 2041697 reaction equation
Cl.[C:2]([N:5]1[C:14]2[C:9](=[CH:10][C:11](Br)=[CH:12][CH:13]=2)[C@H:8]([NH2:16])[CH2:7][C@@H:6]1[CH3:17])(=[O:4])[CH3:3].[CH3:18][N:19]([CH2:27][CH2:28][N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1)[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:2]([N:5]1[C:14]2[C:9](=[CH:10][C:11]([C:32]3[CH:31]=[N:30][N:29]([CH2:28][CH2:27][N:19]([CH3:18])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH:33]=3)=[CH:12][CH:13]=2)[C@H:8]([NH2:16])[CH2:7][C@@H:6]1[CH3:17])(=[O:4])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 67194539HCID 67194539, compoundHCID 68162340HCID 68162340, compound

Product 1

HCID 68162631HCID 68162631, compoundYield 69.6%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(2S,4R)-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (for a preparation see intermediate 57) (1.219 g, 3.81 mmol) and 1,1-dimethylethyl methyl{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethyl}carbamate (for a preparation see intermediate 56) (1.608 g, 4.58 mmol) were combined in 1,4-dioxane (15 mL) and water (5.00 mL) under nitrogen to give a clear yellow solution. Potassium carbonate (1.212 g, 8.77 mmol) then [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.419 g, 0.572 mmol) were added and the resulting red mixture was stirred at 110° C. for 16 h then was cooled to room temperature and concentrated in vacuovacuo. The brown residue was suspended in DCM (20 mL) and filtered through a pad of celite (2 g). The insoluble material was washed with DCM (30 mL) and the combined filtrate and washings were concentrated in vacuovacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient:1 to 10% MeOH in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (1.195 g, 2.66 mmol, 69.6% yield) as a brown foam.

Workup

  1. temperaturethen was cooled to room temperature
  2. concentrationconcentrated in vacuovacuo
  3. filtrationfiltered through a pad of celite (2 g)
  4. washThe insoluble material was washed with DCM (30 mL)
  5. concentrationthe combined filtrate and washings were concentrated in vacuovacuo
  6. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-00683f4f14cc42a793981d01568f2ebe
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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