Sodium Carbonate → HCID 178422652, compound

HRID 1517118Notes

Reaction equation

HRID 1517118 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.[OH:32][C:33]1[N:38]=[C:37]([OH:39])[C:36](B(O)O)=[CH:35][N:34]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[OH:32][C:33]1[N:38]=[C:37]([OH:39])[C:36]([C:2]2[N:7]=[C:6]([C:8]([N:10]3[CH2:15][CH2:14][CH:13]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)[CH2:12][CH2:11]3)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)=[CH:35][N:34]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 44547211[6-Chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneHCID 178514839HCID 178514839, compound

Product 1

HCID 178422652HCID 178422652, compoundYield 15.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 0.20 g (0.44 mmol) of [6-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 3) in 10 ml of 1,2-dimethoxyethane was added 0.138 g (0.88 mmol) of 2,4-dihydroxy-pyrimidine-5-boronic acid, 0.051 g (0.044 mmol) of tetrakis-(triphenylphosphine)-palladium and 0.031 g (0.088 mmol) of 2-(dicyclohexylphosphino)biphenyl, followed by 0.071 g (0.67 mmol) of sodium carbonate and 3.4 ml of H2O. Finally, the reaction mixture was warmed up to 80° C. After 48 hours, it was cooled down to RT, poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1) to give 0.035 g (15%) of the title compound as off-white solid. MS: 528.2 (MH+).

Workup

  1. temperatureit was cooled down to RT
  2. additionpoured
  3. extractionextracted twice with EtOAc
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1)

Sources & evidence

ORD record
ord-ac918452a90142f5ac238c2e7cceb963
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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