Dichloromethane → HCID 118208792, compound

HRID 595271Notes

Reaction equation

HRID 595271 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[CH3:17])[CH:13]=[CH:12][N:11]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][N:31](C(OC(C)(C)C)=O)[CH:32]=2)O1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].O1CCOCC1>[F:18][C:16]([C:14]1[CH:13]=[CH:12][N:11]=[C:10]([NH:9][C:4]2[CH:3]=[C:2]([C:28]3[CH:32]=[N:31][NH:30][CH:29]=3)[CH:7]=[C:6]([CH3:8])[CH:5]=2)[N:15]=1)([F:19])[CH3:17]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118208668HCID 118208668, compound

Product 1

HCID 118208792HCID 118208792, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

N-(3-Bromo-5-methylphenyl)-4-(1,1-difluoroethyl)pyrimidin-2-amine (2.0 g, 6.1 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (1.79 g, 6.09 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.249 g, 0.305 mmol) were combined in a flask. 1,4-Dioxane (30 mL) and aqueous sodium carbonate (9.1 mL, 18.3 mmol, 2.0 M in water) were added, and the resultant suspension was heated to 100° C. for 4 h. The mixture was allowed to cool to room temperature and then filtered, and concentrated under reduced pressure. Purification by gel column chromatography on silica (10-100% ethyl acetate/hexanes) afforded 4-(1,1-difluoroethyl)-N-(3-methyl-5-(1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine as a brown solid. MS ESI calc'd. for C16H16F2N5 [M+H]+ 316. found 316. 1H NMR (500 MHz, DMSO-d6) δ 12.91 (s, 1H), 9.83 (s, 1H), 8.67 (d, J=4.9 Hz, 1H), 8.04 (s, 1H), 7.84 (d, J=18.9 Hz, 1H), 7.78 (s, 1H), 7.32 (s, 1H), 7.08-7.02 (m, 2H), 2.28 (s, 3H), 1.98 (t, J=18.7 Hz, 3H).

Workup

  1. filtrationfiltered
  2. concentrationconcentrated under reduced pressure
  3. customPurification by gel column chromatography on silica (10-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-192099ddce75453494000d818002a9a6
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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