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

HRID 1876598ノート

反応式

HRID 1876598 の反応式
[C:1]([OH:6])(=O)[C@H:2]([CH3:4])[OH:3].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.[CH2:37]([N:41]1[C:49]([N:50]2[CH2:55][CH2:54][NH:53][C@@H:52]([CH3:56])[CH2:51]2)=[N:48][C:47]2[C:42]1=[N:43][C:44]([C:63]1[CH:64]=[N:65][C:66]([NH2:69])=[N:67][CH:68]=1)=[N:45][C:46]=2[N:57]1[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1)[CH:38]([CH3:40])[CH3:39]>C(Cl)Cl.CO.C(Cl)Cl.CN(C)C=O>[NH2:69][C:66]1[N:65]=[CH:64][C:63]([C:44]2[N:43]=[C:42]3[C:47]([N:48]=[C:49]([N:50]4[CH2:55][CH2:54][N:53]([C:1](=[O:6])[C@@H:2]([OH:3])[CH3:4])[C@@H:52]([CH3:56])[CH2:51]4)[N:41]3[CH2:37][CH:38]([CH3:39])[CH3:40])=[C:46]([N:57]3[CH2:62][CH2:61][O:60][CH2:59][CH2:58]3)[N:45]=2)=[CH:68][N:67]=1

参加物

9

反応物 5

HCID 8471Triethylamine2 回HCID 107689L-Lactic Acid2 回HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 27960291-Hydroxybenzotriazole hydrateHCID 593335175-{9-Isobutyl-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

生成物 1

HCID 59333632(2S)-1-{(2S)-4-[2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-morpholin-4-yl-9H-purin-8-yl]-2-methylpiperazin-1-yl}-1-oxopropan-2-ol収率 53%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

L-Lactic acid (29.6 μl, 0.34 mmol), 1-hydroxybenzotriazole monohydrate (43.0 mg, 0.28 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (80.8 mg, 0.42 mmol), and triethylamine (58.8 μl, 0.42 mmol) were added to an N,N-dimethylformamide solution (3.0 ml) of 5-{9-isobutyl-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (127.2 mg, 0.28 mmol) at room temperature. The resulting mixture was stirred for 1 day followed by the addition of L-lactic acid (29.6 μl, 0.34 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (80.8 mg, 0.42 mmol), triethylamine (58.8 μl, 0.42 mmol), and methylene chloride (3.0 ml). The resulting mixture was stirred for 1 day and then the reaction mixture was poured into methylene chloride-methanol (10:1), washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (77.9 mg, 53%) as a pale yellow solid.

後処理

  1. stirringThe resulting mixture was stirred for 1 day
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

出典と根拠

ORDレコード
ord-4c0008f36a37451dbdd311a4d1a39230
出典データセット
uspto-grants-2012_11
特許番号
US08309546B2

反応ノート

読み込み中…