Cesium carbonate → (S)-N4-(1-(5-Fluoropyridin-2-yl)ethyl)-N2-(2-methoxypyridin-3-yl)pyrimidine-2,4-diamine

HRID 573975Notes

Reaction equation

HRID 573975 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])[CH:5]=[CH:4][N:3]=1.[CH3:18][O:19][C:20]1[C:25]([NH2:26])=[CH:24][CH:23]=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C@@H:9]([NH:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:26][C:25]3[C:20]([O:19][CH3:18])=[N:21][CH:22]=[CH:23][CH:24]=3)[N:7]=2)[CH3:10])=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27374883-Amino-2-methoxypyridineHCID 89400369(S)-2-Chloro-N-(1-(5-fluoropyridin-2-yl)ethyl)pyrimidin-4-amine

Product 1

HCID 71245110(S)-N4-(1-(5-Fluoropyridin-2-yl)ethyl)-N2-(2-methoxypyridin-3-yl)pyrimidine-2,4-diamineYield 19%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

An oven-dried resealable Schlenk tube was charged with (S)-2-chloro-N-(1-(5-fluoropyridin-2-yl)ethyl)pyrimidin-4-amine (Preparation 1a, 43 mg, 0.17 mmol), 2-methoxypyridin-3-amine (23 mg, 0.19 mmol), cesium carbonate (111 mg, 0.34 mmol) and 1,4-dioxane (3 mL). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon then tris(dibenzylideneacetone)dipalladium(0) (16 mg, 0.02 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (10 mg, 0.02 mmol) were added. After three further cycles of evacuation-backfilling with argon, the Schlenk tube was capped and then stirred and heated to 100° C. After 24 hours the mixture was cooled to ambient temperature and the solvent was evaporated under reduced pressure. Ethyl acetate was added and the organic solution was washed with water (×3) and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give the title compound (11 mg, 19%) as a solid.

Workup

  1. customAfter three further cycles of evacuation-backfilling with argon, the Schlenk tube was capped
  2. temperatureAfter 24 hours the mixture was cooled to ambient temperature
  3. customthe solvent was evaporated under reduced pressure
  4. additionEthyl acetate was added
  5. washthe organic solution was washed with water (×3) and brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-2a5e8161a4b043159915d0f1b10ad627
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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