Sodium Carbonate → Ethyl 3-hydroxy-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-3-yl]cyclopentanecarboxylate

HRID 2207374Notes

Reaction equation

HRID 2207374 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Br[C:29]1[CH:30]=[C:31]([C:35]2([OH:45])[CH2:39][CH2:38][CH:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:36]2)[CH:32]=[N:33][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.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].C(Cl)Cl>[OH:45][C:35]1([C:31]2[CH:32]=[N:33][CH:34]=[C:29]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[N:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][N:19]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)[CH:30]=2)[CH2:39][CH2:38][CH:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:36]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 131735895Ethyl 3-(5-bromo-3-pyridinyl)-3-hydroxycyclopentanecarboxylate

Product 1

HCID 131735896Ethyl 3-hydroxy-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-3-yl]cyclopentanecarboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (211 mg, 0.557 mmol), ethyl 3-(5-bromopyridin-3-yl)-3-hydroxycyclopentanecarboxylate (175 mg, 0.557 mmol), and sodium carbonate (2 M, 557 μl, 1.11 mmol) in 2-methyl THF (2785 μl) was purged with argon for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (22.7 mg, 0.028 mmol) was added to the reaction mixture and heated to 85° C. overnight. Upon cooling, the reaction was diluted with water and extracted with DCM (3×). The combined organic layers were dried under reduced pressure and purified by silica gel chromatography (ethyl acetate/hexanes) to afford ethyl 3-hydroxy-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-3-yl]cyclopentanecarboxylate. MS ESI calc'd for C25H26F3N4O3 [M+H]+ 487. found 487.

Workup

  1. customwas purged with argon for 10 minutes
  2. temperatureUpon cooling
  3. extractionextracted with DCM (3×)
  4. customThe combined organic layers were dried under reduced pressure
  5. custompurified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8d7dea164fec49d08f2e34116b3b9349
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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