2-Amino-3-Hydroxypyridine → HCID 67244132, compound

HRID 2421901Notes

Reaction equation

HRID 2421901 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][O:14][C:13]3[N:17]=[CH:18][C:19]([C:21](Cl)=[O:22])=[CH:20][C:12]2=3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:24][C:25]1[C:30](O)=[CH:29][CH:28]=[CH:27][N:26]=1.CCN(C(C)C)C(C)C.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1.C(Cl)Cl.C(=O)(O)[O-].[Na+]>[O:22]1[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24]=[C:21]1[C:19]1[CH:18]=[N:17][C:13]2[O:14][CH2:15][CH2:16][N:11]([S:8]([C:5]3[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=3)(=[O:10])=[O:9])[C:12]=2[CH:20]=1

Participants

8

Reactant 4

HCID 281142-Amino-3-HydroxypyridineHCID 81531DiisopropylethylamineHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 86634653HCID 86634653, compound

Product 1

HCID 67244132HCID 67244132, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

1-(4-fluorophenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride (25 mg, 70 μmol) was dissolved in THF (0.5 mL) and placed in a 2 mL microwave vial. To this solution was added 2-aminopyridin-3-ol (8.5 mg, 77 μmol), DIPEA (26 μL, 150 μmol) and a magnetic stirrer bar and the reaction was capped. After stirring at room temperature for 1 hour, conversion to the amide was complete as shown by LCMS. To the crude reaction mixture was added Burgess reagent (83 mg, 350 μmol) and the reaction was heated for 5 minutes at 150° C. on a Biotage Initiator. The reaction mixture was diluted with DCM (3 mL) and saturated aqueous sodium bicarbonate (3 mL). The organic layer was removed and the aqueous layer extracted with DCM (2 mL). The organic layers were combined, dried with sodium sulfate, filtered and evaporated to produce a brown oil that was purified by flash column chromatography on an ISCO HPLC using a 4 gram SiO2 cartridge and a gradient of 25-100% hexanes in EtOAc. This yielded 15 mg (52%) of a yellow oil. LCMS (+ESI) m/z=413.0 [M+H]+; 1H-NMR (CDCl3) δ 9.05 (dd, 2H), 8.60 (d, 1H), 7.95 (dd, 1H), 7.82 (d, 1H), 7.78 (d, 1H), 7.35 (dd, 1H), 7.20 (dd, 2H), 4.12 (t, 2H), 3.96 (t, 2H).

Workup

  1. customthe reaction was capped
  2. customTo the crude reaction mixture
  3. temperaturethe reaction was heated for 5 minutes at 150° C. on a Biotage Initiator
  4. customThe organic layer was removed
  5. extractionthe aqueous layer extracted with DCM (2 mL)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto produce a brown oil that
  10. customwas purified by flash column chromatography on an ISCO HPLC

Sources & evidence

ORD record
ord-f2940473764d488789231f9d5d3f05ba
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

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