Triethylamine → (2S)-1-(4-{2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-9H-purin-8-yl}piperazin-1-yl)-1-oxopropan-2-ol

HRID 421441ノート

反応式

HRID 421441 の反応式
[CH2:1]([N:5]1[C:13]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:12][C:11]2[C:6]1=[N:7][C:8]([C:27]1[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=1)=[N:9][C:10]=2[N:20]1[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]1[CH3:26])[CH:2]([CH3:4])[CH3:3].[OH:34][C@@H:35]([CH3:39])[C:36](O)=[O:37].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl>[NH2:33][C:30]1[N:31]=[CH:32][C:27]([C:8]2[N:7]=[C:6]3[C:11]([N:12]=[C:13]([N:14]4[CH2:19][CH2:18][N:17]([C:36](=[O:37])[C@@H:35]([OH:34])[CH3:39])[CH2:16][CH2:15]4)[N:5]3[CH2:1][CH:2]([CH3:4])[CH3:3])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]3[CH3:26])[N:9]=2)=[CH:28][N:29]=1

参加物

9

反応物 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 107689L-Lactic AcidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593335555-{9-Isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-8-piperazin-1-yl-9H-purin-2-yl}pyrimidin-2-amine

生成物 1

HCID 59333666(2S)-1-(4-{2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-9H-purin-8-yl}piperazin-1-yl)-1-oxopropan-2-ol収率 46.2%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒

実験手順

A methylene chloride (5 ml) solution of 5-{9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-8-piperazin-1-yl-9H-purin-2-yl}pyrimidin-2-amine (119 mg, 0.26 mmol), (S)-2-hydroxypropionic acid (28 mg, 0.32 mmol), 1-hydroxybenzotriazole (35 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg, 0.32 mmol), and triethylamine (55 μl, 0.39 mmol) was stirred at room temperature for 2 days. Chloroform and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture and the resulting mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and, after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography (chloroform:methanol=96:4) to give a solid. The resulting solid was purified by flash NH silica gel column chromatography (methylene chloride:methanol=99:1) to give the title compound (63 mg, 46%) as a solid.

後処理

  1. extractionthe resulting mixture was extracted with chloroform
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationafter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash silica gel column chromatography (chloroform:methanol=96:4)
  6. customto give a solid
  7. customThe resulting solid was purified by flash NH silica gel column chromatography (methylene chloride:methanol=99:1)

出典と根拠

ORDレコード
ord-b887cb90c0714d15b32dcf5d8fb6a77c
出典データセット
uspto-grants-2012_01
特許番号
US08097622B2

反応ノート

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