Sodium Carbonate → N-(3-(1-(2-amino ethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride

HRID 595166Notes

Reaction equation

HRID 595166 reaction equation
O1CCOCC1.[F:7][CH:8]([F:32])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]2[CH:21]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:19]=[C:18]([CH3:31])[CH:17]=2)[N:10]=1.[Cl:33][C:34]1[CH:35]=[N:36][N:37]([CH2:39][CH2:40][NH:41]C(=O)OC(C)(C)C)[CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[ClH:33].[NH2:41][CH2:40][CH2:39][N:37]1[CH:38]=[C:34]([C:20]2[CH:21]=[C:16]([NH:15][C:11]3[N:10]=[C:9]([CH:8]([F:7])[F:32])[CH:14]=[CH:13][N:12]=3)[CH:17]=[C:18]([CH3:31])[CH:19]=2)[CH:35]=[N:36]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 584561714-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 130164691tert-butyl (2-(4-chloro-1H-pyrazol-1-yl)ethyl)carbamate

Product 1

HCID 118208517N-(3-(1-(2-amino ethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

1,4-Dioxane (40 mL) and water (9 mL) were added to a flask containing 4-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (3.00 g, 8.31 mmol), tert-butyl (2-(4-chloro-1H-pyrazol-1-yl)ethyl)carbamate (3.06 g, 12.5 mmol), SiliaCat Si-DPP-Pd (9.58 g, 2.49 mmol, 0.26 mmol/g), and sodium carbonate (4.40 g, 41.5 mmol). The reaction was heated at 110° C. overnight. The reaction mixture was filtered, washed with 1,4-dioxane, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes) and dissolved in a small amount of 1,4-dioxane. Hydrochloric acid (4N in 1,4-dioxane, 10 mL) in was added and the mixture was allowed to stir for 3 hours. The mixture was diluted with diethyl ether, filtered, washed with diethyl ether, and dried over anhydrous sodium sulfate to afford N-(3-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride. MS ESI calc'd. for C17H19F2N6 [M+H]+ 345. found 345. 1H NMR (500 MHz, DMSO-d6): δ 9.92 (s, 1H), 8.68 (d, J=4.9 Hz, 1H), 8.29 (s, 3H), 8.15 (s, 1H), 7.87 (s, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 7.04 (t, J=5.3 Hz, 2H), 6.89 (t, J=54.5 Hz, 1H), 4.42 (t, J=6.3 Hz, 2H), 3.27-3.25 (m, 2H), 2.28 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with 1,4-dioxane
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes)
  5. dissolutiondissolved in a small amount of 1,4-dioxane
  6. additionHydrochloric acid (4N in 1,4-dioxane, 10 mL) in was added
  7. additionThe mixture was diluted with diethyl ether
  8. filtrationfiltered
  9. washwashed with diethyl ether
  10. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-b9bef87ebe96415da2d3be32c284d4a1
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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