Triethylamine → HCID 59333681, compound

HRID 421351Notes

Reaction equation

HRID 421351 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(OC([NH:70][CH2:71][C:72](O)=[O:73])=O)(C)(C)C>ClCCl.CO.CN(C)C=O>[NH2:70][CH2:71][C:72]([N:47]1[CH2:48][CH2:49][N:44]([C:43]2[N:35]([CH2:34][CH:31]3[CH2:32][CH2:33]3)[C:36]3[C:41]([N:42]=2)=[C:40]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[N:39]=[C:38]([C:56]2[CH:61]=[N:60][C:59]([NH2:62])=[N:58][CH:57]=2)[N:37]=3)[CH2:45][CH2:46]1)=[O:73]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 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 59333681HCID 59333681, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

1-Hydroxybenzotriazole monohydrate (33.8 mg, 0.22 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (63.4 mg, 0.33 mmol), and triethylamine (82.9 μl, 0.60 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 (96.2 mg, 0.22 mmol) and N-tert-butoxycarbonyl-glycine (46.3 mg, 0.26 mmol) at room temperature. The resulting mixture was stirred for 3 days and then the reaction mixture was poured into dichloromethane-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 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 the 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 then 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 (19.1 mg, 18%) as a pale yellow solid.

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate 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. additionthe concentrated, dichloromethane was added to the residue
  9. extractionThe resulting mixture was extracted with dichloromethane-methanol (10:1)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltrated
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customthe resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1)

Sources & evidence

ORD record
ord-f7ad92890db547528fe018a7cd279c83
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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