Hydrochloric Acid → HCID 58466186, compound

HRID 335936Notes

Reaction equation

HRID 335936 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C@@:21]4([CH2:25][O:24][C:23]([NH2:26])=[N:22]4)[C:20]4[C:15](=[N:16][CH:17]=[C:18]([C:27]#[C:28][C:29]5([CH3:33])[CH2:32][O:31][CH2:30]5)[CH:19]=4)[O:14][C:11]3=[CH:12][CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.O.[ClH:35].C(OCC)(=O)C>CC#N.C(=O)(O)[O-].[Na+]>[NH2:26][C:23]1[O:24][CH2:25][C@:21]2([C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:27]#[C:28][C:29]([CH2:32][Cl:35])([CH3:33])[CH2:30][OH:31])[CH:19]=3)[O:14][C:11]3[C:10]2=[CH:9][C:8]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:13][CH:12]=3)[N:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 45254510HCID 45254510, compound

Product 1

HCID 58466186HCID 58466186, compoundYield 53.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

To a slurry of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (500 mg, 1.13 mmol, Example 78) in 10 mL of MeCN was added 10 mL of water followed by 1 mL of 6 N HCl. The resulting solution was heated at 50° C. overnight. The reaction was cooled to rt, diluted with saturated sodium bicarbonate (100 mL) and poured into a separatory funnel containing ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (1×50 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a white solid that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% DCM to 10:1 methanol in DCM with 0.1% ammonium hydroxide) to provide 4-((S)-2′-amino-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-(chloromethyl)-2-methylbut-3-yn-1-ol (290 mg, 0.606 mmol, 53.6% yield) as a white solid.

Workup

  1. temperatureThe reaction was cooled to rt
  2. additionpoured into a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (1×50 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialbrine, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a white solid
  10. customthat was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% DCM to 10:1 methanol in DCM with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-177f1003f20c4920a0564bea2c883646
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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