Triethylamine → HCID 59333607, compound

HRID 1876540Notes

Reaction equation

HRID 1876540 reaction equation
O.ON1C2C=CC=CC=2N=N1.Cl.CN(CCCN=C=NCC)C.C(N(CC)CC)C.[CH:31]1([CH2:34][N:35]2[C:43]([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)=[N:42][C:41]3[C:36]2=[N:37][C:38]([C:56]2[CH:57]=[N:58][C:59]([NH2:62])=[N:60][CH:61]=2)=[N:39][C:40]=3[N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[CH2:33][CH2:32]1.C(O[C:68]([N:70](C)[CH2:71][C:72](O)=[O:73])=O)(C)(C)C>ClCCl.CO.CN(C)C=O>[CH:31]1([CH2:34][N:35]2[C:43]([N:44]3[CH2:49][CH2:48][N:47]([C:72](=[O:73])[CH2:71][NH:70][CH3:68])[CH2:46][CH2:45]3)=[N:42][C:41]3[C:36]2=[N:37][C:38]([C:56]2[CH:61]=[N:60][C:59]([NH2:62])=[N:58][CH:57]=2)=[N:39][C:40]=3[N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[CH2:32][CH2:33]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 593335735-[9-(Cyclopropylmethyl)-6-morpholin-4-yl-8-piperazin-1-yl-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 59333607HCID 59333607, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

1-Hydroxybenzotriazole monohydrate (35.1 mg, 0.23 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (65.9 mg, 0.34 mmol), and triethylamine (86.2 μl, 0.62 mmol) were added to an N,N-dimethylformamide suspension (2.0 ml) of 5-[9-(cyclopropylmethyl)-6-morpholin-4-yl-8-piperazin-1-yl-9H-purin-2-yl]pyrimidin-2-amine (100.0 mg, 0.23 mmol) and N-tert-butoxycarbonyl-N-methylglycine (52.0 mg, 0.27 mmol) at room temperature. The resulting mixture was stirred for 3 days and the reaction mixture was poured into dichloromethane-methanol (10:1), washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was dissolved in dichloromethane (4.0 ml) followed by the addition of trifluoroacetic acid (2.0 ml) with ice cooling. The resulting mixture was stirred at room temperature for 2 hours and concentrated, dichloromethane was added to the residue, and the resulting mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution. The resulting mixture was extracted with dichloromethane-methanol (10:1), dried over anhydrous sodium sulfate, and filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1) to give the title compound (67.1 mg, 58%) as a pale yellow solid.

Workup

  1. washwashed with saturated aqueous sodium bicarbonate solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionthe resulting residue was dissolved in dichloromethane (4.0 ml)
  6. additionfollowed by the addition of trifluoroacetic acid (2.0 ml) with ice cooling
  7. stirringThe resulting mixture was stirred at room temperature for 2 hours
  8. concentrationconcentrated
  9. additiondichloromethane was added to the residue
  10. extractionThe resulting mixture was extracted with dichloromethane-methanol (10:1)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltrated
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1)

Sources & evidence

ORD record
ord-dd2033dea224463592b67725149b37a9
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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