Oxalyl chloride → (E)-N-(3-(6-amino-7-(4-chlorophenyl)-8-oxo-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamide

HRID 1887047Notes

Reaction equation

HRID 1887047 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.[NH2:17][C:18]1[N:26]=[CH:25][N:24]=[C:23]2[C:19]=1[N:20]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)[C:21](=[O:34])[N:22]2[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([NH2:33])[CH:28]=1>C(#N)C.CN(C=O)C.C(Cl)Cl>[NH2:17][C:18]1[N:26]=[CH:25][N:24]=[C:23]2[C:19]=1[N:20]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)[C:21](=[O:34])[N:22]2[C:27]1[CH:28]=[C:29]([NH:33][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 3

HCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 866912156-amino-9-(3-aminophenyl)-7-(4-chlorophenyl)-7H-purin-8(9H)-one

Product 1

HCID 71666598(E)-N-(3-(6-amino-7-(4-chlorophenyl)-8-oxo-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamideYield 19.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt (94 mg, 0.57 mmol) in dry acetonitrile (5 mL) was added 1 drop of DMF before introducing (COCl)2 (0.5 mL, 5.3 mmol). Resulting mixture was stirred at room temperature for 1 hour. Concentrated and dissolved in dry DCM (2 mL) before introducing a solution of 6-amino-9-(3-aminophenyl)-7-(4-chlorophenyl)-7H-purin-8(9H)-one (13) (100 mg, 0.28 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 (0.3% Et3N)) followed by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3.H2O)) to give (E)-N-(3-(6-amino-7-(4-chlorophenyl)-8-oxo-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamide (14) (25 mg, 19.1%) as a white solid. LC-MS (ESI): m/z (M/M+2) 464/466. 1H NMR (400 MHz, DMSO) δ 10.57 (s, 1H), 9.82 (s, 1H), 8.11 (s, 1H), 7.99 (s, 1H), 7.71 (d, J=8.5 Hz, 1H), 7.62 (d, J=8.7 Hz, 2H), 7.56-7.45 (m, 3H), 7.35 (d, J=8.8 Hz, 1H), 6.82-6.65 (m, 1H), 6.46 (d, J=15.3 Hz, 1H), 5.98 (s, 2H), 4.01-3.87 (m, 2H), 2.79 (s, 3H), 2.78 (s, 3H).

Workup

  1. customResulting mixture
  2. concentrationConcentrated
  3. dissolutiondissolved in dry 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 (0.3% Et3N))

Sources & evidence

ORD record
ord-a2a2711139d54331a363ba538242192d
Source dataset
uspto-grants-2013_08
Patent number
US08501724B1

Reaction notes

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