1,4-Dioxane → HCID 58504409, compound

HRID 2367175Notes

Reaction equation

HRID 2367175 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[F:12])#[N:2].Cl[C:14]1[N:19]=[C:18]([NH2:20])[N:17]=[C:16]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=1.O1CCOCC1.C([O-])(O)=O.[Na+]>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.O>[NH2:20][C:18]1[N:19]=[C:14]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:12])[CH:5]=2)[CH:15]=[C:16]([NH:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:17]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 14842704-N-benzyl-6-chloropyrimidine-2,4-diamineHCID 2783130(4-Cyano-3-fluorophenyl)boronic acid

Product 1

HCID 58504409HCID 58504409, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To (4-cyano-3-fluorophenyl)boronic acid (190 mg, 1.15 mmol) and 6-chloro-N4-(phenylmethyl)-2,4-pyrimidinediamine (300 mg, 1.28 mmol) into a sealable flask were added 1,4-dioxane (6 mL) and saturated aqueous NaHCO3 (3 mL). The mixture was degassed with nitrogen gas for 10 minutes. Pd(Ph3P)4 (74 mg, 0.064 mmol) was added and the reaction mixture was stirred overnight at 100° C. The mixture was poured onto EtOAc and water. The organic layer was separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were filtered, then washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH). The material (367 mg) was carried on as is into the next reaction.

Workup

  1. customThe mixture was degassed with nitrogen gas for 10 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted with EtOAc
  4. filtrationThe combined organic layers were filtered
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH)
  10. customas is into the next reaction

Sources & evidence

ORD record
ord-c35ce1a2ac3f4d74a372ec195843b441
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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