Nitrogen → 5-(3-Chloro-2-methoxy-4-pyridinyl)-N4-(4,4-dimethylcyclohexyl)-2,4-pyrimidinediamine

HRID 876022Notes

Reaction equation

HRID 876022 reaction equation
[CH3:1][C:2]1([CH3:17])[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[C:14](I)=[CH:13][N:12]=[C:11]([NH2:16])[N:10]=2)[CH2:4][CH2:3]1.[Cl:18][C:19]1[C:20]([O:28][CH3:29])=[N:21][CH:22]=[CH:23][C:24]=1B(O)O.N#N.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(O)=O.[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[Cl:18][C:19]1[C:20]([O:28][CH3:29])=[N:21][CH:22]=[CH:23][C:24]=1[C:14]1[C:9]([NH:8][CH:5]2[CH2:6][CH2:7][C:2]([CH3:17])([CH3:1])[CH2:3][CH2:4]2)=[N:10][C:11]([NH2:16])=[N:12][CH:13]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 441198093-Chloro-2-methoxypyridine-4-boronic acidHCID 58299664N4-(4,4-dimethylcyclohexyl)-5-iodo-2,4-pyrimidinediamine

Product 1

HCID 583000415-(3-Chloro-2-methoxy-4-pyridinyl)-N4-(4,4-dimethylcyclohexyl)-2,4-pyrimidinediamineYield 81.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a 50 mL single-necked round bottom flask were placed compound 326 (0.80 g, 2.3 mmol), 3-chloro-2-methoxypyridin-4-ylboronic acid (1.3 g, 6.9 mmol), and trans-dichlorobis(triphenyl-phosphine)palladium (ii) (0.16 g, 0.23 mmol). The flask was subjected to 3 cycles of evacuation and back-filling with N2. 1,4-Dioxane (12 mL) was added followed with sodium carbonate (2 N aqueous solution) (5.8 mL, 12 mmol). The resulting mixture was heated in an oil bath at 80° C. for 18 h. Upon workup, the mixture was poured into ice and saturated NaHCO3 aqueous solution and extracted with ethyl acetate (3×). The combined organics were dried over Na2SO4 and concentrated in vacuo. The residue was subjected to combi-flash column chromatography (methanol/DCM) to give compound 332 (0.68 g, 81% yield) as a light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.09 (1 H, d, J=5.1 Hz), 7.48 (1 H, s), 6.92 (1 H, d, J=5.1 Hz), 6.13 (2 H, s), 5.79 (1 H, d, J=8.3 Hz), 3.91-4.02 (4 H, m), 1.26-1.63 (6 H, m), 1.13-1.25 (2 H, m), 0.88 (6 H, d, J=9.8 Hz). LCMS-ESI (POS), M/Z, M+1: Found 362.0.

Workup

  1. customTo a 50 mL single-necked round bottom flask were placed
  2. extractionextracted with ethyl acetate (3×)
  3. dry with materialThe combined organics were dried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23a24b9ba7c242caa6b65486b060f131
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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