Sodium Carbonate → HCID 131735898, compound

HRID 2207380Notes

Reaction equation

HRID 2207380 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:28][C:29]1[CH:30]=[C:31]([NH:44][C:45]2[N:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:48]=[CH:47][N:46]=2)[CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1>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.O1CCOCC1>[OH:21][C:8]1([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:33]3[CH:32]=[C:31]([NH:44][C:45]4[N:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:48]=[CH:47][N:46]=4)[CH:30]=[C:29]([CH3:28])[CH:34]=3)[CH:3]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 17758932HCID 17758932, compoundHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 131735898HCID 131735898, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Dioxane (2.70 mL), tert-butyl 4-(5-bromopyridin-3-yl)-4-hydroxypiperidine-1-carboxylate (207 mg, 0.580 mmol), and sodium carbonate (2 M, 791 μL, 1.58 mmol) was added to N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (200 mg, 0.527 mmol) and purged and flushed with Ar(g) (3×). PdCl2(dppf)-dichloromethane adduct (21.5 mg, 0.026 mmol) was added to the reaction mixture and heated to 100° C. for 8 hours. The reaction mixture was cooled to room temperature, filtered through CELITE, washed with dichloromethane and extracted with water. The organic layer was dried over sodium sulfate, and was concentrated under reduced pressure. The residue was purified by silica gel chromatography (acetone/hexanes) to yield tert-butyl 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-3-yl]piperidine-1-carboxylate. MS APCI calc'd for C27H31F3N5O3 [M+H]+ 530. found 530.

Workup

  1. custompurged
  2. customflushed with Ar(g) (3×)
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered through CELITE
  5. washwashed with dichloromethane
  6. extractionextracted with water
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationwas concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (acetone/hexanes)

Sources & evidence

ORD record
ord-520944733da64993aa883303049af18e
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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