Potassium Carbonate → HCID 67243137, compound

HRID 1970405Notes

Reaction equation

HRID 1970405 reaction equation
[C:1](=[O:4])([O-])[O-:2].[K+].[K+].[F:7][C:8]1[C:13](B(O)O)=[CH:12][CH:11]=[CH:10][N:9]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.[F:32][C:33]([F:64])([F:63])S(O[C:38]1[CH:51]=[C:50]2[C:41]([O:42][C:43]3[CH:44]=[CH:45][C:46]([N:57]4[CH2:62][CH2:61][O:60][CH2:59][CH2:58]4)=[CH:47][C:48]=3[C@@:49]32[CH2:55][O:54][C:53]([NH2:56])=[N:52]3)=[CH:40][CH:39]=1)(=O)=O>O1CCOCC1.C(OCC)(=O)C.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.O>[F:32][C:33]([F:64])([F:63])[C:1]([OH:2])=[O:4].[F:7][C:8]1[C:13]([C:38]2[CH:39]=[CH:40][C:41]3[O:42][C:43]4[C:48](=[CH:47][C:46]([N:57]5[CH2:58][CH2:59][O:60][CH2:61][CH2:62]5)=[CH:45][CH:44]=4)[C@:49]4([CH2:55][O:54][C:53]([NH2:56])=[N:52]4)[C:50]=3[CH:51]=2)=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 27832702-Fluoropyridine-3-boronic acid2×HCID 86640737HCID 86640737, compound

Product 1

HCID 67243137HCID 67243137, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 0.5-2 ml microwave vial was charged with potassium carbonate (59.8 mg, 0.433 mmol), 2-fluoropyridin-3-ylboronic acid (34.5 mg, 0.245 mmol) and AmPhos (5.11 mg, 7.21 μmol). A solution of (R)-2-amino-2′-morpholino-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (70 mg, 0.144 mmol) in dioxane (841 μL) was added followed by water (120 μL). Rhe vial was sealed and heated in microwave reactor at 100° C. for 1 hr. Tetrakis(triphenylphosphine)palladium(0) (16.66 mg, 0.014 mmol) and 2-fluoropyridin-3-ylboronic acid (34.5 mg, 0.245 mmol) were added and the mixture was heated for 30 min at 110 C in the microwave reactor. The dark brown mixture was diluted with 3 ml of ethyl acetate, filtered through celite and concentrated. The mixture was purified by silica gel chromatography on 12 g RediSep column using 15-60% DCM/MeOH/NH4OH in DCM. The derived residue was then purified by reverse phase HPLC (15-90% MeCN in 0.1% aq. TFA) to afford (S)-2′-(2-fluoropyridin-3-yl)-7′-morpholino-5H-spiro[oxazole-4,9′-xanthen]-2-amine 2,2,2-trifluoroacetate as an off white solid. Found MS: MH+=441.

Workup

  1. customRhe vial was sealed
  2. temperaturethe mixture was heated for 30 min at 110 C in the microwave reactor
  3. filtrationfiltered through celite
  4. concentrationconcentrated
  5. customThe mixture was purified by silica gel chromatography on 12 g RediSep column
  6. customThe derived residue was then purified by reverse phase HPLC (15-90% MeCN in 0.1% aq. TFA)

Sources & evidence

ORD record
ord-b25e502432894300bb0ed10893a43a71
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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