Pyridine → 3-Amino-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-one

HRID 1052961Notes

Reaction equation

HRID 1052961 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3(O)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:5]([CH3:24])[O:4][N:3]=1.[N:25]1C=CC=CC=1.O=S(Cl)Cl>C1COCC1.N.CO.CC(=O)OCC>[NH2:25][C:10]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:24])[CH:8]=2)[NH:12][C:11]1=[O:16]

Participants

7

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 862961015-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one

Product 1

HCID 862808213-Amino-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-oneYield 40%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21705897Ammonia methanolSolvent

Procedure

Under N2, to a solution of 5-(3,5-dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one (21 g, 65.6 mmol, 1.0 eq) in THF (300 mL) was added dropwise pyridine (30 mL) and SOCl2 (15 mL) at −15° C.˜−20° C., the mixture was stirred for 20 min at −15° C.˜−20° C., quenched with brine (50 mL), washed with brine (300 mL×2), the organic phase was concentrated to give 17.5 g crude product. The crude product was dissolved in NH3/MeOH (7M, 200 mL), and stirred for 2 hours at room temperature. Then the solvent was removed in vacuo to give crude product, which was dissolved in EA (200 mL), washed with water (100 mL), then brine (100 mL), dried over Na2SO4, concentrated to give 15 g crude product, which was purified by sili-gel to give 8.5 g (yield 40%) product as white solid. 1H NMR (DMSO-d6) δH 10.53 (s, 1H), 7.39-7.41 (d, 2H, J=8.0 Hz), 7.29-7.33 (t, 2H, J=8.0 Hz), 7.21-7.26 (m, 2H), 7.14 (s, 1H), 6.98-7.00 (d, 1H, J=8.0 Hz), 2.75 (s, 2H), 2.33 (s, 3H), 2.16 (s, 3H)

Workup

  1. customquenched with brine (50 mL)
  2. washwashed with brine (300 mL×2)
  3. concentrationthe organic phase was concentrated
  4. customto give 17.5 g crude product
  5. stirringstirred for 2 hours at room temperature
  6. customThen the solvent was removed in vacuo
  7. customto give crude product, which
  8. washwashed with water (100 mL)
  9. dry with materialbrine (100 mL), dried over Na2SO4
  10. concentrationconcentrated
  11. customto give 15 g crude product, which
  12. customwas purified by sili-gel

Sources & evidence

ORD record
ord-d9a1443afa534d709b87d33325077b96
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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