3-Isoxazolamine → HCID 117737157, compound

HRID 1504443Notes

Reaction equation

HRID 1504443 reaction equation
[C:1]([CH2:3][O:4][C:5]1[C:6]([N:19]2[C:28]3[C:23](=[CH:24][C:25]([S:29](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:31])=[O:30])=[CH:26][CH:27]=3)[CH:22]=[CH:21][C:20]2=[O:44])=[CH:7][C:8]([F:18])=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:10]=1)#[N:2].[O:45]1[CH:49]=[CH:48][C:47]([NH2:50])=[N:46]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[C:1]([CH2:3][O:4][C:5]1[C:6]([N:19]2[C:28]3[C:23](=[CH:24][C:25]([S:29]([NH:50][C:47]4[CH:48]=[CH:49][O:45][N:46]=4)(=[O:31])=[O:30])=[CH:26][CH:27]=3)[CH:22]=[CH:21][C:20]2=[O:44])=[CH:7][C:8]([F:18])=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:10]=1)#[N:2]

Participants

5

Reactant 3

HCID 18102163-IsoxazolamineHCID 2733832Lithium Hexamethyldisilazide2×HCID 117736900HCID 117736900, compound

Product 1

HCID 117737157HCID 117737157, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, a solution of perfluorophenyl 1-(5-(cyanomethoxy)-2,3′-difluoro-[1,1′-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (250 mg, 0.394 mmol), isoxazol-3-amine (40.8 μl, 0.552 mmol) and THF (3940 μl) was cooled in an ice-bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF, 985 μl, 0.985 mmol) was added dropwise. The whole was warmed to rt and stirred for 30 min. An additional 1 mL of 1M LHMDS in THF was added and stirred for 30 min. The whole was quenched with 0.2 mL of TFA and concentrated. The product was purified further by RPLC on the acidic Gilson. Fractions containing the product were combined and concentrated. Precipitate was filtered with an aid of water, dried to afford pink solid. m/z (ESI), [M+H]+=535.2. 1H NMR (500 MHz, DMSO-d6) δ ppm 5.11-5.33 (m, 2 H) 6.45 (d, J=1.76 Hz, 1 H) 6.77-6.96 (m, 2 H) 7.28-7.46 (m, 1 H) 7.50-7.59 (m, 2H) 7.59-7.72 (m, 3 H) 7.87 (dd, J=8.98, 2.08 Hz, 1 H) 8.26 (d, J=9.83 Hz, 1H) 8.40 (d, J=2.03 Hz, 1 H) 8.73 (d, J=1.76 Hz, 1 H) 11.66 (br. s., 1 H).

Workup

  1. stirringstirred for 30 min
  2. customThe whole was quenched with 0.2 mL of TFA
  3. concentrationconcentrated
  4. customThe product was purified further by RPLC on the acidic Gilson
  5. additionFractions containing the product
  6. concentrationconcentrated
  7. filtrationPrecipitate was filtered with an aid of water
  8. customdried
  9. customto afford pink solid

Sources & evidence

ORD record
ord-df33dae448d5486c868ef1101f1422df
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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