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

HRID 1876604

反応式

HRID 1876604 の反応式
ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C.[CH:33]1([CH2:36][N:37]2[C:45]([N:46]3[CH2:51][CH2:50][NH:49][C@H:48]([CH3:52])[CH2:47]3)=[N:44][C:43]3[C:38]2=[N:39][C:40]([C:59]2[CH:60]=[N:61][C:62]([NH2:65])=[N:63][CH:64]=2)=[N:41][C:42]=3[N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)[CH2:35][CH2:34]1.[C:66](O)(=[O:70])[C@@H:67]([CH3:69])[OH:68]>C(Cl)Cl.CO.C(Cl)Cl.CN(C)C=O>[NH2:65][C:62]1[N:63]=[CH:64][C:59]([C:40]2[N:39]=[C:38]3[C:43]([N:44]=[C:45]([N:46]4[CH2:51][CH2:50][N:49]([C:66](=[O:70])[C@H:67]([OH:68])[CH3:69])[C@H:48]([CH3:52])[CH2:47]4)[N:37]3[CH2:36][CH:33]3[CH2:35][CH2:34]3)=[C:42]([N:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)[N:41]=2)=[CH:60][N:61]=1

参加物

9

反応物 5

HCID 8471TriethylamineHCID 10868Dicyclohexylcarbodiimide2 回HCID 61503D-Lactic AcidHCID 757711-HydroxybenzotriazoleHCID 593335225-{9-(cyclopropylmethyl)-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

生成物 1

HCID 59333577(2R)-1-{(2R)-4-[2-(2-Aminopyrimidin-5-yl)-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-8-yl]-2-methylpiperazin-1-yl}-1-oxopropan-2-ol収率 76%

試薬・触媒・溶媒 3

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

実験手順

1-Hydroxybenzotriazole (33.2 mg, 0.25 mmol), N,N′-dicyclohexylcarbodiimide (76.1 mg, 0.37 mmol), and triethylamine (102.8 μl, 0.75 mmol) were added to an N,N-dimethylformamide (3.0 ml)-methylene chloride (3.0 ml) mixture solution of 5-{9-(cyclopropylmethyl)-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (110.8 mg, 0.25 mmol) and D-lactic acid (26.9 mg, 0.30 mmol) at room temperature. The resulting mixture was stirred for 18.5 hours followed by the addition of N,N′-dicyclohexylcarbodiimide (76.1 mg, 0.37 mmol) and the resulting mixture stirred at 40° C. for 22 hours. 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 (98.1 mg, 76%) as a pale yellow solid.

後処理

  1. stirringthe resulting mixture stirred at 40° C. for 22 hours
  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-667cfbd0da4d4ae0a82a081a20e4ea19
出典データセット
uspto-grants-2012_11
特許番号
US08309546B2

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