Methanol → (S)-3-(3-methoxy-3-methylbut-1-ynyl)-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 1970360Notes

Reaction equation

HRID 1970360 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]#[C:21][C:22]([CH3:25])([OH:24])[CH3:23])[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([C:26]2[CH:27]=[N:28][CH:29]=[N:30][CH:31]=2)=[CH:10][CH:11]=3)[N:6]=1.CO.[CH3:34]S(O)(=O)=O>C(=O)(O)[O-].[Na+]>[CH3:34][O:24][C:22]([CH3:25])([CH3:23])[C:21]#[C:20][C:17]1[CH:18]=[C:19]2[C@:5]3([CH2:4][O:3][C:2]([NH2:1])=[N:6]3)[C:7]3[C:12](=[CH:11][CH:10]=[C:9]([C:26]4[CH:27]=[N:28][CH:29]=[N:30][CH:31]=4)[CH:8]=3)[O:13][C:14]2=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 67383136(S)-4-(2'-amino-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

Product 1

HCID 58466315(S)-3-(3-methoxy-3-methylbut-1-ynyl)-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (S)-4-(2′-amino-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-methylbut-3-yn-2-ol (58 mg, 0.140 mmol) in MeOH (1703 μL, 42.1 mmol) was added methane sulfonic acid (91 μL, 1.403 mmol) in a vial. The vial was sealed and placed in a 70° C. oil bath for 3 hours. The mixture was poured into saturated aqueous sodium bicarbonate solution (20 mL) and extracted with DCM (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 25-g SNAP column, eluting with 0-70% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM to give (S)-3-(3-methoxy-3-methylbut-1-ynyl)-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid after evaporation from DCM/hexane.

Workup

  1. customThe vial was sealed
  2. customplaced in a 70° C.
  3. customfor 3 hours
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography on a 25-g SNAP column
  9. washeluting with 0-70% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-231e9720cfab4c5a80e9be9140a73fd0
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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