Acetonitrile → (E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide

HRID 1887056Notes

Reaction equation

HRID 1887056 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].C(Cl)(C(Cl)=O)=O.NC1[N:26]=[CH:25][N:24]=[C:23]2C=1[N:20]([C:36]1[CH:41]=[CH:40][C:39]([O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:38][CH:37]=1)[C:21](=[O:35])[N:22]2[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([NH:33][CH3:34])[CH:28]=1.[C:49](#[N:51])[CH3:50]>CN(C=O)C.C(Cl)Cl>[NH2:51][C:49]1[N:26]=[CH:25][N:24]=[C:23]2[C:50]=1[N:20]([C:36]1[CH:41]=[CH:40][C:39]([O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:38][CH:37]=1)[C:21](=[O:35])[N:22]2[C:27]1[CH:28]=[C:29]([N:33]([CH3:34])[C:7](=[O:8])/[CH:6]=[CH:5]/[CH2:4][N:3]([CH3:10])[CH3:2])[CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 866912206-amino-9-(3-(methylamino)phenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one

Product 1

HCID 71666739(E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamideYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt (95 mg, 0.57 mmol) in acetonitrile (5 mL) was added 1 drop of DMF before introducing (COCl)2 (0.25 mL, 2.86 mmol). Resulting mixture was stirred at room temperature for 2 hours. Concentrated and dissolved in DCM (2 mL) before introduced to the solution of 6-amino-9-(3-(methylamino)phenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one (32) (100 mg, 0.24 mmol) in DCM (2 mL). Resulting solution was stirred at room temperature for 2 hours before quenched the reaction with MeOH (2 mL). Solvent was removed and the residue was pre-purified by column chromatography (silica gel, 0 to 10% methanol in methylene chloride (1% Et3N)) followed by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3)) to give (E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide (33) (60 mg, 47%) as white solid. LC-MS (ESI): m/z (M+1) 536. 1H NMR (400 MHz, DMSO) δ 8.11 (s, 1H), 7.72-7.56 (m, 3H), 7.51-7.33 (m, 5H), 7.23-7.09 (m, 5H), 6.65 (dt, J=15.2, 6.1 Hz, 1H), 6.04 (d, J=16.6 Hz, 1H), 5.90 (br, 2H), 3.27 (s, 3H), 2.99 (s, 2H), 2.10 (s, 6H).

Workup

  1. customResulting mixture
  2. concentrationConcentrated
  3. dissolutiondissolved in DCM (2 mL)
  4. stirringResulting solution was stirred at room temperature for 2 hours
  5. custombefore quenched
  6. customthe reaction with MeOH (2 mL)
  7. customSolvent was removed
  8. customthe residue was pre-purified by column chromatography (silica gel, 0 to 10% methanol in methylene chloride (1% Et3N))

Sources & evidence

ORD record
ord-a76d96be2de64b39bddaf19b7b128887
Source dataset
uspto-grants-2013_08
Patent number
US08501724B1

Reaction notes

Loading…