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

반응식

HRID 1876604 반응식
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

참가 물질

9

반응물 5

HCID 8471TriethylamineHCID 10868Dicyclohexylcarbodiimide2회HCID 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

생성물 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-ol수율 76%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 21226129Dichloromethane methanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-667cfbd0da4d4ae0a82a081a20e4ea19
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309546B2

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