Diisopropylethylamine → HCID 178462813, compound

HRID 1884915Notes

Reaction equation

HRID 1884915 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]#[C:10][C:11]([OH:13])=O.C(N(C(C)C)CC)(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.[NH2:43][C:44]1[CH:45]=[C:46]([NH:50][C:51]2[N:59]=[C:58]([NH:60][CH:61]3[CH2:66][CH2:65][CH:64]([OH:67])[CH2:63][CH2:62]3)[N:57]=[C:56]3[C:52]=2[N:53]=[CH:54][N:55]3[CH2:68][CH3:69])[CH:47]=[CH:48][CH:49]=1>CN(C=O)C.C(#N)C>[CH2:68]([N:55]1[CH:54]=[N:53][C:52]2[C:56]1=[N:57][C:58]([NH:60][C@H:61]1[CH2:66][CH2:65][C@H:64]([OH:67])[CH2:63][CH2:62]1)=[N:59][C:51]=2[NH:50][C:46]1[CH:45]=[C:44]([NH:43][C:11](=[O:13])[C:10]#[C:9][C:3]2[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH:49]=[CH:48][CH:47]=1)[CH3:69]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium Tetrafluoroborate2×HCID 23504692trans-4-[6-(3-amino-phenylamino)-9-ethyl-9H-purin-2-yl-amino]-cyclohexanolHCID 23504704HCID 23504704, compound3×

Product 1

HCID 178462813HCID 178462813, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent5×HCID 6342AcetonitrileSolvent3×

Procedure

To a solution of 4.3 g (0.02 mol) (2,6-dichlorophenyl)-propargylic acid (M. S. Reich et al., Bull. Soc. Chim. Fr. 21, 217-225 (1917)) in 120 ml DMF and 120 ml acetonitrile are added at RT 4.23 ml (0.025 mol) N,N-di-isopropyl-N-ethylamine, followed by a solution of 5.94 g (0.02 mol) TPTU (O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, Fluka, Buchs, Switzerland) in 100 ml DMF. The resulting solution is stirred at RT for 5 minutes and then added dropwise to a solution of 7.36 g (0.02 mol) 4-[6-(3-amino-phenylamino)-9-ethyl-9H-purin-2-ylamino]-cyclohexanol (example 77, stage 1.2) in a 1:1 mixture of DMF and acetonitrile (240 ml). The addition takes 1.25 hrs and stirring at RT is continued for an additional hour. A second portion of preactivated (2,6-dichlorophenyl)-propargylic acid [prepared by adding 2.0 g (0.0066 mol) TPTU in 30 ml DMF to a solution of 1.3 g (0.0066 mol) (2,6-dichlorophenyl)-propargylic acid in 30 ml DMF and 30 ml acetonitrile and stirring for 5 minutes at RT] was then added dropwise over 30 minutes. After stirring for another 1.5 hrs the solvent is evaporated under reduced pressure and the residue taken up in a mixture of ethyl acetate and 10% aqueous citric acid. The aqueous phase is extracted with ethyl acetate and the combined organic layers are washed with water, saturated sodium bicarbonate solution and brine. After drying (anhydrous sodium sulfate) the ethyl acetate solution is concentrated until the product crystallises. It is collected by filtration, re-suspended in a small amount of ethyl acetate, filtered and vacuum dried. N-{3-[9-Ethyl-2-(trans-4-hydroxy-cyclo-hexylamino)-9H-purin-6-yl-amino]-phenyl}-3-(2,6-dichlorophenyl)-propargylic acid amide (7.0 g, 60%), is obtained as a colourless solid.

Workup

  1. additionThe addition
  2. waittakes 1.25 hrs
  3. stirringstirring at RT
  4. waitis continued for an additional hour
  5. stirringstirring for 5 minutes at RT]
  6. additionwas then added dropwise over 30 minutes
  7. stirringAfter stirring for another 1.5 hrs the solvent
  8. customis evaporated under reduced pressure
  9. additionthe residue taken up in a mixture of ethyl acetate and 10% aqueous citric acid
  10. extractionThe aqueous phase is extracted with ethyl acetate
  11. washthe combined organic layers are washed with water, saturated sodium bicarbonate solution and brine
  12. dry with materialAfter drying (anhydrous sodium sulfate) the ethyl acetate solution
  13. concentrationis concentrated until the product
  14. customcrystallises
  15. filtrationIt is collected by filtration
  16. filtrationfiltered
  17. customvacuum dried

Sources & evidence

ORD record
ord-f23aceabffb844b1b2bfe74d96bb4d0b
Source dataset
uspto-grants-2004_07
Patent number
US06767906B2

Reaction notes

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