Pyridine → HCID 117668357, compound

HRID 1052969Notes

Reaction equation

HRID 1052969 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([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)O)=[C:5]([CH3:25])[O:4][N:3]=1.[N:26]1C=CC=CC=1.O=S(Cl)Cl>C1COCC1>[NH2:26][C:10]1([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=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[CH3:25])[CH:8]=2)[NH:12][C:11]1=[O:16]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 86282448HCID 86282448, compound

Product 1

HCID 117668357HCID 117668357, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under N2, to a solution of 5-(3,5-dimethylisoxazol-4-yl)-3-(4-fluorophenyl)-3-hydroxyindolin-2-one (52 g, 154 mmol, 1.0 eq) in THF (500 mL) was added pyridine (40 mL, 496 mmol, 3.2 eq) and SOCl2 (16 mL, 219 mmol, 1.4 eq) slowly at −15° C.˜−20° C., the mixture was stirred for 20 min at −15° C.˜−20° C., quenched with brine, washed with brine (300 mL×2), to the THF layer was added NH3/H2O (100 mL), the mixture was stirred for 2 hours at room temperature, washed with brine, dried, concentrated, purified by silicon gel to give a crude product which was recrystallized from i-PrOH/toluene to give 14 g (yield 27%) product as white solid. 1H NMR (DMSO-d6) δH 10.57 (s, 1H), 7.40-7.44 (m, 2H), 7.22-7.24 (dd, 1H, J=8.0 Hz, 1.6 Hz), 7.11-7.16 (m, 3H), 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
  2. washwashed with brine (300 mL×2), to the THF layer
  3. additionwas added NH3/H2O (100 mL)
  4. stirringthe mixture was stirred for 2 hours at room temperature
  5. washwashed with brine
  6. customdried
  7. concentrationconcentrated
  8. custompurified by silicon gel
  9. customto give a crude product which
  10. customwas recrystallized from i-PrOH/toluene

Sources & evidence

ORD record
ord-c6c90c4718d949d0834d4e510bedcf78
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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