Sodium Carbonate → ((2S)-6-(5-amino-1-cyclopropyl-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

HRID 1051685Notes

Reaction equation

HRID 1051685 reaction equation
[CH:1]1([O:5][C:6]2[C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=[C:12]3[C:7]=2[CH2:8][CH2:9][C@H:10]([CH3:30])[N:11]3[C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH2:4][CH2:3][CH2:2]1.[CH:31]1([N:34]2[C:38]([NH2:39])=[C:37](I)[CH:36]=[N:35]2)[CH2:33][CH2:32]1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O>[NH2:39][C:38]1[N:34]([CH:31]2[CH2:33][CH2:32]2)[N:35]=[CH:36][C:37]=1[C:15]1[C:6]([O:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:25]([CH:27]1[CH2:29][CH2:28]1)=[O:26])[C@@H:10]([CH3:30])[CH2:9][CH2:8]2

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 1180757251-cyclopropyl-4-iodo-1H-pyrazol-5-amineHCID 123998323(2S)-5-cyclobutoxy-1-cyclopropanecarbonyl-2-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline

Product 1

HCID 118075398((2S)-6-(5-amino-1-cyclopropyl-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A 50-mL round-bottom flask was charged with (S)-(5-cyclobutoxy-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.140 g, 0.34 mmol), 1-cyclopropyl-4-iodo-1H-pyrazol-5-amine (0.071 g, 0.29 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (23.2 mg, 0.03 mmol, 0.10 equiv), sodium carbonate (0.061 g, 0.58 mmol), 1,4-dioxane (10 mL) and water (3 mL). The resulting mixture stirred for 18 h at 80° C. and was then cooled to room temperature. The reaction mixture was filtered through a short pad of Celite, and the filtrate was concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:5, ethyl acetate/petroleum ether) to afford ((2S)-6-(5-amino-1-cyclopropyl-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.025 g (20%) as light yellow oil. MS (ESI, pos. ion) m/z 407 [M+H]+.

Workup

  1. temperaturewas then cooled to room temperature
  2. filtrationThe reaction mixture was filtered through a short pad of Celite
  3. concentrationthe filtrate was concentrated under vacuum
  4. customThe residue was purified via column chromatography on silica gel (eluting with 1:5, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-758d95fd0f5a44cba1ec5402d25c444e
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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