Triethylamine → (2S)-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 421402Notes

Reaction equation

HRID 421402 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 593335225-{9-(cyclopropylmethyl)-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

Product 1

HCID 45376242(2S)-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-olYield 41.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

L-Lactic acid (26.8 μl, 0.30 mmol), 1-hydroxybenzotriazole monohydrate (38.9 mg, 0.25 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.0 mg, 0.38 mmol), and triethylamine (53.0 μl, 0.38 mmol) were added to an N,N-dimethylformamide solution (2.0 ml) of 5-{9-(cyclopropylmethyl)-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (114.3 mg, 0.25 mmol) at room temperature. The resulting mixture was stirred for 20 hours followed by the addition of L-lactic acid (26.8 μl, 0.30 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.0 mg, 0.38 mmol), and triethylamine (53.0 μl, 0.38 mmol) and the resulting mixture was stirred for 3 days. L-Lactic acid (26.8 μl, 0.30 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (73.0 mg, 0.38 mmol), and triethylamine (53.0 μl, 0.38 mmol) were further added, the resulting mixture was stirred for 2 days, and 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 (54.3 mg, 41%) 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 (methylene chloride:methanol=10:1)

Sources & evidence

ORD record
ord-548fde1e5c99450daf3535df57fa96af
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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