Triethylamine → HCID 45376367, compound

HRID 421413Notes

Reaction equation

HRID 421413 reaction equation
[C:1]([OH:6])(=O)[C@H:2]([CH3:4])[OH:3].O.ON1C2C=CC=CC=2N=N1.Cl.CN(CCCN=C=NCC)C.C(N(CC)CC)C.[CH3:37][C@H:38]1[NH:43][CH2:42][CH2:41][N:40]([C:44]2[N:45]([CH2:66][C:67]([F:70])([F:69])[F:68])[C:46]3[C:51]([N:52]=2)=[C:50]([N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)[N:49]=[C:48]([C:59]2[CH:60]=[N:61][C:62]([NH2:65])=[N:63][CH:64]=2)[N:47]=3)[CH2:39]1>C(Cl)Cl.CO.CN(C)C=O.C(Cl)Cl>[NH2:65][C:62]1[N:63]=[CH:64][C:59]([C:48]2[N:47]=[C:46]3[C:51]([N:52]=[C:44]([N:40]4[CH2:41][CH2:42][N:43]([C:1](=[O:6])[C@@H:2]([OH:3])[CH3:4])[C@H:38]([CH3:37])[CH2:39]4)[N:45]3[CH2:66][C:67]([F:69])([F:68])[F:70])=[C:50]([N:53]3[CH2:54][CH2:55][O:56][CH2:57][CH2:58]3)[N:49]=2)=[CH:60][N:61]=1

Participants

9

Reactant 5

HCID 8471Triethylamine2×HCID 107689L-Lactic Acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrateHCID 593335845-{8-[(3R)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine

Product 1

HCID 45376367HCID 45376367, compoundYield 36.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

L-Lactic acid (48.2 μl, 0.55 mmol), 1-hydroxybenzotriazole monohydrate (42.0 mg, 0.27 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (105.1 mg, 0.55 mmol), and triethylamine (76.4 μl, 0.55 mmol) were added to a methylene chloride (3.0 ml)-N,N-dimethylformamide (3.0 ml) mixture solution of 5-{8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (131.1 mg, 0.27 mmol) at room temperature. The resulting mixture was stirred for 5 days followed by the addition of L-lactic acid (48.2 μl, 0.55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (105.1 mg, 0.55 mmol), and triethylamine (76.4 μl, 0.55 mmol). 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 (53.9 mg, 36%) as a pale yellow solid.

Workup

  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)

Sources & evidence

ORD record
ord-ecbce31e7a214032ace7c3bced7ac50e
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

Loading…