Lithium Chloride → (S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-(pyrimidin-2-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335920Notes

Reaction equation

HRID 335920 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:26]4[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:16][C:17]=3[C@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[C:9]([F:33])[CH:8]=1)(=O)=O.C([Sn](CCCC)(CCCC)[C:41]1[N:46]=[CH:45][CH:44]=[CH:43][N:42]=1)CCC.[Cl-].[Li+]>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.[Cu]I.CN(C=O)C>[F:33][C:9]1[C:10]2[O:11][C:12]3[C:17](=[CH:16][C:15]([C:26]4[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:14][CH:13]=3)[C@@:18]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:19]=2[CH:20]=[C:7]([C:41]2[N:42]=[CH:43][CH:44]=[CH:45][N:46]=2)[CH:8]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 86640722(S)-2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 1

HCID 53464878(S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-(pyrimidin-2-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amineYield 46.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A microwave vial was charged with (S)-2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (100 mg, 0.195 mmol), tetrakis(triphenylphosphine)palladium(0) (22.51 mg, 0.019 mmol), copper(i) iodide (3.71 mg, 0.019 mmol), 2-(tributylstannyl)pyrimidine (216 mg, 0.584 mmol) and DMF (974 μL). Lithium chloride (83 mg, 1.948 mmol) was added, the vial was flushed with argon, sealed and heated at 85° C. for 4 hrs. The mixture was cooled to the room temperature, diluted with water (1 ml) and ethyl acetate (3 ml). The organic layer was loaded onto 2 g SCX-2 column and washed with ethyl acetate and methanol. The material was released from the column using 2 M ammonia in MeOH solution. The filtrated was concentrated and purified by silica gel chromatography (10-80% CH2Cl2/MeOH/NH4OH in CH2Cl2) to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(pyrimidin-2-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (40 mg, 0.090 mmol).

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. temperatureThe mixture was cooled to the room temperature
  4. additiondiluted with water (1 ml) and ethyl acetate (3 ml)
  5. washwashed with ethyl acetate and methanol
  6. concentrationThe filtrated was concentrated
  7. custompurified by silica gel chromatography (10-80% CH2Cl2/MeOH/NH4OH in CH2Cl2)

Sources & evidence

ORD record
ord-10dbaa55f71145b1b4660ed9b0fbfe2b
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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