Tetrahydrofuran → HCID 25261307, compound

HRID 1517336Notes

Reaction equation

HRID 1517336 reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].C1COCC1.[CH2:17]([S:19]([C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([C:31]1[CH:36]=[C:35]([O:37][CH:38]3[CH2:43][CH2:42][N:41]([C:44](N4C=CN=C4)=[O:45])[CH2:40][CH2:39]3)[N:34]=[CH:33][N:32]=1)[CH2:26][CH2:25]2)(=[O:21])=[O:20])[CH3:18]>O>[CH2:17]([S:19]([C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([C:31]1[N:32]=[CH:33][N:34]=[C:35]([O:37][CH:38]3[CH2:39][CH2:40][N:41]([C:44]([O:5][CH:1]4[CH2:4][CH2:3][CH2:2]4)=[O:45])[CH2:42][CH2:43]3)[CH:36]=1)[CH2:26][CH2:25]2)(=[O:20])=[O:21])[CH3:18]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 76218CyclobutanolHCID 23665647Potassium tert-butoxideHCID 68563270HCID 68563270, compound

Product 1

HCID 25261307HCID 25261307, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Cyclobutanol (90 μL, 1.15 mmol) and potassium tert-butoxide (50 mg, 0.446 mmol) were added to a THF (2.5 mL) suspension of the 5-(ethylsulfonyl)-1-(6-{[1-(1H-imidazol-1-ylcarbonyl)piperidin-4-yl]oxy}pyrimidin-4-yl)indoline (109 mg, 0.226 mmol) produced in Reference Example 31, and the mixture was stirred at room temperature for 1 hour. To the reaction solution, water was added, followed by extraction with ethyl acetate three times. The obtained organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [(i) hexane:ethyl acetate=50:50, V/V; (ii) ethyl acetate]. The obtained crude product was washed with diisopropyl ether to obtain the title compound as white powder (34.6 mg, yield: 32%).

Workup

  1. customproduced in Reference Example 31
  2. extractionfollowed by extraction with ethyl acetate three times
  3. washThe obtained organic layer was washed with water and saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography [(i) hexane:ethyl acetate=50:50, V/V; (ii) ethyl acetate]
  7. customThe obtained crude product
  8. washwas washed with diisopropyl ether

Sources & evidence

ORD record
ord-a07b9d0b7d0343a3b073323f12b9342d
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

Loading…