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

HRID 1517332ノート

反応式

HRID 1517332 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-6c4c9997ab0548ff86ca92bf975cb618
出典データセット
uspto-grants-2012_07
特許番号
US08232287B2

反応ノート

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