Dichloromethane → HCID 178492162, compound

HRID 1811880Notes

Reaction equation

HRID 1811880 reaction equation
C(N(CC)CC)C.[CH3:8][C:9](OC(C)=O)=[O:10].[CH3:15][O:16][C:17]1[N:22]=[CH:21][C:20]([NH:23][C:24]2[C:29]([C:30]3[N:38]=[C:37]([CH3:39])[N:36]=[C:35]4[C:31]=3[N:32]=[CH:33][NH:34]4)=[CH:28][C:27]([CH2:40][N:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)=[CH:26][N:25]=2)=[CH:19][CH:18]=1.C(Cl)Cl>CN(C=O)C.[NH4+].[Cl-].O.CCOC(C)=O>[CH3:15][O:16][C:17]1[N:22]=[CH:21][C:20]([NH:23][C:24]2[N:25]=[CH:26][C:27]([CH2:40][N:41]3[CH2:42][CH2:43][N:44]([C:9](=[O:10])[CH3:8])[CH2:45][CH2:46]3)=[CH:28][C:29]=2[C:30]2[N:38]=[C:37]([CH3:39])[N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][NH:34]3)=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 178492161HCID 178492161, compound

Product 1

HCID 178492162HCID 178492162, compoundYield 56.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

Triethylamine (42.2 mg, 0.417 mmol) and Ac2O (0.013 mL, 0.139 mmol) were added to a stirred solution of N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-(piperazin-1-ylmethyl)pyridin-2-amine (60 mg, 0.139 mmol) in DCM (3 mL, 46.6 mmol) and DMF (0.5 mL, to improve solubility) at room temperature. The mixture was stirred for 1 h and then diluted with NH4Cl(aq), water (10 mL) and EtOAc (10 mL each). The separated aqueous layer was extracted with EtOAc (3×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was heated at 60° C. with excess of Na2CO3 (50 mg) in CH3CN (5 mL) and water (1 mL) for 2 h. The resulting suspension was concentrated and washed with a minimal amount of cold MeOH to give 1-(4-((6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)methyl)piperazin-1-yl)ethanone (37 mg, 56%) as a yellow solid. LCMS (API-ES) m/z 474 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 13.63 (br. s., 1H) 12.64 (br. s., 1H) 9.73 (br. s., 1H) 8.60 (s, 1H) 8.54 (br. s., 1H) 8.03-8.30 (m, 2H) 6.85 (d, J=8.61 Hz, 1H) 3.85 (s, 3H) 3.53 (br. s., 2H) 3.39-3.49 (m, 4H) 2.85 (s, 3H) 2.25-2.46 (m, 4H) 1.97 (s, 3H).

Workup

  1. extractionThe separated aqueous layer was extracted with EtOAc (3×15 mL)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. concentrationThe resulting suspension was concentrated
  6. washwashed with a minimal amount of cold MeOH

Sources & evidence

ORD record
ord-89c82619e8e74a51aa11613db1545d95
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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