Triethylamine → (2S)-1-{(2S)-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 1876588Notes

Reaction equation

HRID 1876588 reaction equation
[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.[CH:37]1([CH2:40][N:41]2[C:49]([N:50]3[CH2:55][CH2:54][NH:53][C@@H:52]([CH3:56])[CH2:51]3)=[N:48][C:47]3[C:42]2=[N:43][C:44]([C:63]2[CH:64]=[N:65][C:66]([NH2:69])=[N:67][CH:68]=2)=[N:45][C:46]=3[N:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)[CH2:39][CH2:38]1>C(Cl)Cl.CO.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[CH2:40][CH:37]3[CH2:39][CH2:38]3)=[C:46]([N:57]3[CH2:62][CH2:61][O:60][CH2:59][CH2:58]3)[N:45]=2)=[CH:68][N:67]=1

Participants

8

Reactant 5

HCID 8471Triethylamine3×HCID 107689L-Lactic Acid3×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 27960291-Hydroxybenzotriazole hydrateHCID 593335285-{9-(Cyclopropylmethyl)-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

Product 1

HCID 45376104(2S)-1-{(2S)-4-[2-(2-Aminopyrimidin-5-yl)-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-8-yl]-2-methylpiperazin-1-yl}-1-oxopropan-2-olYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

L-Lactic acid (27.1 μl, 0.31 mmol), 1-hydroxybenzotriazole monohydrate (39.3 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.8 mg, 0.38 mmol), and triethylamine (53.6 μl, 0.38 mmol) were added to an N,N-dimethylformamide solution (2.0 ml) of 5-{9-(cyclopropylmethyl)-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (115.6 mg, 0.26 mmol) at room temperature. The resulting mixture was stirred for 20 hours followed by the addition of L-lactic acid (27.1 μl, 0.31 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.8 mg, 0.38 mmol), and triethylamine (53.6 μl, 0.38 mmol) and the resulting mixture was stirred for 3 days. L-Lactic acid (27.1 μl, 0.31 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.8 mg, 0.38 mmol), and triethylamine (53.6 μl, 0.38 mmol) were further added, the resulting mixture was stirred for 2 days, 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 (double development with methylene chloride:methanol=15:1) to give the title compound (89.7 mg, 67%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was stirred for 3 days
  2. stirringthe resulting mixture was stirred for 2 days
  3. washwashed with saturated aqueous sodium hydrogen carbonate solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by preparative thin layer silica gel chromatography (double development with methylene chloride:methanol=15:1)

Sources & evidence

ORD record
ord-f56b3614be954d1784ab397d7b110cef
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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