Triethylamine → HCID 59333679, compound

HRID 421349Notes

Reaction equation

HRID 421349 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.Cl.[CH3:64][N:65]([CH3:70])[CH2:66][C:67](O)=[O:68]>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:67](=[O:68])[CH2:66][N:65]([CH3:70])[CH3:64])[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 8471Triethylamine2×HCID 75605N,N-Dimethylglycine hydrochlorideHCID 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 59333679HCID 59333679, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
50 °C

Procedure

1-Hydroxybenzotriazole monohydrate (35.0 mg, 0.23 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (65.7 mg, 0.34 mmol), and triethylamine (38.2 μl, 0.27 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 (99.7 mg, 0.23 mmol) and N,N-dimethylglycine hydrochloride (38.3 mg, 0.27 mmol) at room temperature. The resulting mixture was stirred for 20.5 hours and heated to 50° C. followed by the addition of triethylamine (38.2 μl, 0.27 mmol) and the resulting mixture was stirred for 6 hours. The resulting mixture was further stirred at room temperature for 17 hours 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 purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1) to give the title compound (84.6 mg, 71%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was stirred for 6 hours
  2. stirringThe resulting mixture was further stirred at room temperature for 17 hours
  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 (dichloromethane:methanol=5:1)

Sources & evidence

ORD record
ord-5405d78cde004a94b63c9279f8a61f3a
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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