Acetonitrile → HCID 56971567, compound

HRID 2278452Notes

Reaction equation

HRID 2278452 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[CH:6][N:5]=[C:4]([N:15]2[CH2:20][C@H:19]([CH3:21])[O:18][C@H:17]([CH3:22])[CH2:16]2)[N:3]=1.[C:23]1([CH3:32])[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].CC#N>O1CCOCC1.O.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>[CH3:22][C@H:17]1[O:18][C@@H:19]([CH3:21])[CH2:20][N:15]([C:4]2[N:3]=[C:2]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[CH3:32])[C:7]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=3)=[CH:6][N:5]=2)[CH2:16]1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 86702425cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholine

Product 1

HCID 56971567HCID 56971567, compoundYield 30.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

To a suspension of cis-4-(4-chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholine (0.100 g, 0.314 mmol), o-tolylboronic acid (0.064 g, 0.471 mmol) and potassium carbonate (0.138 g, 1 mmol) in 1,4-dioxane (3 mL) and water (0.5 mL) stirred in air at 20° C. was added solid tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.0500 mmol). The reaction mixture was stirred under nitrogen at 100° C. overnight. The reaction mixture was allowed to cool to room temperature, diluted with water and extracted with ethyl acetate (×3). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The crude product was purified by pre-HPLC, (Gilson GX-281; Shimadzu 15 um 250*19 mm; A:10 mMol NH4HCO3/Water B: CH3CN; 0-7 min 85-95%, 7-14 min 95%; 214 nm; 30 mL/min) to obtain the title compound (35.4 mg, 0.095 mmol, 30.1% yield). LC/MS [M+H]+=375; 1H NMR (400 MHz, CDCl3): δ 8.41 (1H, s), 8.27-8.25 (1H, s), 7.29-7.25 (1H, m), 7.17-7.14 (2H, m), 7.10-7.09 (1H, m), 6.81 (1H, s), 6.69-6.67 (1H, d), 4.69-4.65 (2H, d), 3.72-3.63 (2H, m), 2.69-2.63 (2H, m), 2.43 (3H, s), 2.07 (3H, s), 1.27-1.26 (6H, d).

Workup

  1. stirringThe reaction mixture was stirred under nitrogen at 100° C. overnight
  2. temperatureto cool to room temperature
  3. extractionextracted with ethyl acetate (×3)
  4. customdried under magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe crude product was purified by pre-HPLC, (Gilson
  7. custom0-7 min 85-95%, 7-14 min 95%

Sources & evidence

ORD record
ord-4846a88359494e8dba864a0414db21b5
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

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