3-Hydroxybutyric Acid → 4-[4-({6-[5-(Methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidin-1-yl]-4-oxobutan-2-ol

HRID 1517332Notes

Reaction equation

HRID 1517332 reaction equation
[OH:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=O.C(N(C(C)C)CC)(C)C.[Cl-].COC1N=C([N+]2(C)CCOCC2)N=C(OC)N=1.Cl.[CH3:36][S:37]([C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[N:45]([C:49]1[CH:54]=[C:53]([O:55][CH:56]3[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]3)[N:52]=[CH:51][N:50]=1)[CH2:44][CH2:43]2)(=[O:39])=[O:38]>O.C(O)C>[CH3:36][S:37]([C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[N:45]([C:49]1[N:50]=[CH:51][N:52]=[C:53]([O:55][CH:56]3[CH2:61][CH2:60][N:59]([C:4](=[O:6])[CH2:3][CH:2]([OH:1])[CH3:7])[CH2:58][CH2:57]3)[CH:54]=1)[CH2:44][CH2:43]2)(=[O:39])=[O:38]

Participants

7

Reactant 4

HCID 4413-Hydroxybutyric AcidHCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 685639645-(Methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride

Product 1

HCID 685621764-[4-({6-[5-(Methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidin-1-yl]-4-oxobutan-2-olYield 69.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

3-hydroxybutanoic acid (61 μL, 0.66 mmol), diisopropylethylamine (102 μL, 0.571 mmol), and 4-(dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (235 mg, 0.849 mmol) were added to an ethanol (3 mL) suspension of the 5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride (224 mg, 0.545 mmol) produced in Reference Example 27, and the mixture was stirred at room temperature for 3 days. To the reaction solution, water was added, followed by extraction with dichloromethane three times. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by thin-layer silica gel chromatography (dichloromethane:methanol=1:1, V/V). The obtained crude product was washed with diisopropyl ether to obtain the title compound as grayish white foam (174 mg, yield: 69%).

Workup

  1. customproduced in Reference Example 27
  2. extractionfollowed by extraction with dichloromethane three times
  3. washThe obtained organic layer was washed with 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 thin-layer silica gel chromatography (dichloromethane:methanol=1:1, V/V)
  7. customThe obtained crude product
  8. washwas washed with diisopropyl ether

Sources & evidence

ORD record
ord-6c4c9997ab0548ff86ca92bf975cb618
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

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