Dimethylformamide → (S)-2-amino-2'-(neopentyloxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-1'-carbonitrile

HRID 335780Notes

Reaction equation

HRID 335780 reaction equation
Br[C:2]1[C:15]2[C@:14]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:12]=3)[O:7][C:6]=2[CH:5]=[CH:4][C:3]=1[O:27][CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30].[C:33]([Zn]C#N)#[N:34].CN(C=O)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>[NH2:20][C:17]1[O:18][CH2:19][C@@:14]2([N:16]=1)[C:15]1[C:2]([C:33]#[N:34])=[C:3]([O:27][CH2:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH:4]=[CH:5][C:6]=1[O:7][C:8]1[C:13]2=[CH:12][C:11]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 58466130(S)-1'-bromo-2'-(neopentyloxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amineHCID 178514179HCID 178514179, compound

Product 1

HCID 58466277(S)-2-amino-2'-(neopentyloxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-1'-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A vial was charged with (S)-1′-bromo-2′-(neopentyloxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (68.1 mg, 0.138 mmol), dicyanozinc (81 mg, 0.689 mmol), tetrakis(triphenylphosphine)palladium(0) (31.8 mg, 0.028 mmol), and DMF (689 μL). The vial was sealed and placed in a 120° C. oil bath for 12 hours. The mixture was diluted with water and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on a 25-g SNAP column, eluting with a 90:10:1 mix of DCM/MeOH/NH4OH in DCM. This gave ca. 40 mg of a white powder that was impure by HPLC. The solid was combined with 104487-6-2 in DMSO/MeOH and purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA). The fractions containing product were combined in saturated aq. sodium bicarbonate solution with the aid of methanol and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give (S)-2-amino-2′-(neopentyloxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-1′-carbonitrile as an off-white powder after evaporation from DCM/hexane.

Workup

  1. customThe vial was sealed
  2. customplaced in a 120° C.
  3. customfor 12 hours
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed on a 25-g SNAP column
  9. washeluting with a 90:10:1
  10. additionmix of DCM/MeOH/NH4OH in DCM
  11. custompurified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA)
  12. additionThe fractions containing product
  13. extractionextracted with DCM (3×)
  14. dry with materialThe combined organic extracts were dried over sodium sulfate
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-f223de34d9b24e6d8fd8dfff9ce99e15
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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