Tetrahydrofuran → (S)-2-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)benzonitrile

HRID 1970300Notes

Reaction equation

HRID 1970300 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:29]=1)[C:18]1[CH:17]=[C:16](Br)[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([O:20][C:21]2[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=2[C:23]#[N:24])=[CH:9][CH:10]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.C1COCC1.C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=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>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:29]=1)[C:18]1[CH:17]=[C:16]([C:32]3[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=3)[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([O:20][C:21]2[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=2[C:23]#[N:24])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 67242927(R)-2-(2-amino-2'-bromo-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)benzonitrile

Product 1

HCID 58466265(S)-2-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)benzonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with (R)-2-(2-amino-2′-bromo-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)benzonitrile (75 mg, 0.167 mmol), pyridin-3-ylboronic acid (51.4 mg, 0.418 mmol), tetrakis(triphenylphosphine)palladium(0) (9.67 mg, 8.37 μmol), THF (837 μL), and potassium carbonate (418 μL, 0.837 mmol) (as a 2.0 M aq. solution). The vial was sealed and heated to 100° C. in a shaker overnight. The mixture was diluted with EtOAc and the layers were separated. The aqueous layer was extracted with EtOAc (2×). The combined organic extracts were evaporated, and the residue was chromatographed on a 25-g SNAP column, eluting with 0-80% of a 90:10:1 mix of DCM/MeOH/NH4OH in DCM to give (S)-2-(2-amino-2′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)benzonitrile as a pale-yellow solid.

Workup

  1. customThe vial was sealed
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. customThe combined organic extracts were evaporated
  5. customthe residue was chromatographed on a 25-g SNAP column
  6. washeluting with 0-80% of a 90:10:1
  7. additionmix of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-9017db2a79004ff9b0cb589bf0ad8b5c
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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