Cesium carbonate → HCID 58102791, compound

HRID 450198Notes

Reaction equation

HRID 450198 reaction equation
CN[C@@H]1CCCC[C@H]1NC.[F:11][CH:12]([F:39])[C:13]1[N:17]([C:18]2[N:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)[C:16]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:15]=2[N:14]=1.Br[C:41]1[CH:42]=[N:43][CH:44]=[N:45][CH:46]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl.[Cu]I>[F:39][CH:12]([F:11])[C:13]1[N:17]([C:18]2[N:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][N:22]3[C:41]2[CH:42]=[N:43][CH:44]=[N:45][CH:46]=2)[C:16]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:15]=2[N:14]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178488369HCID 178488369, compound

Product 1

HCID 58102791HCID 58102791, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
102.5 °C

Procedure

trans-N,N′-Dimethylcyclohexane-1,2-diamine (0.071 mL, 0.450 mmol) in DMF (5 mL) was added to a mixture of 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-2-(4-morpholinyl)-9H-purine (180 mg, 0.448 mmol), 5-bromopyrimidine (356 mg, 2.24 mmol), CuI (85 mg, 0.448 mmol), and Cs2CO3 (321 mg, 0.986 mmol) under nitrogen, and the mixture was heated at 100-105° C. for 3 days. The mixture was cooled to room temperature, diluted with CH2Cl2, and filtered through celite. The celite plug was washed with CH2Cl2 and CH2Cl2/MeOH (9:1) before the solvents were removed under vacuum. Chromatography on silica, eluting with hexanes/EtOAc (70:30 to 20:80), followed by recrystallization from EtOAc/hexanes, gave 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-2-(4-morpholinyl)-9-(5-pyrimidinyl)-9H-purine (113 mg, 53%): mp (EtOAc/hexanes) 238-240° C.; 1H NMR (CDCl3) δ 9.47 (s, 2H), 9.30 (s, 1H), 8.89 (s, 1H), 7.53 (t, JHF=52.6 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.29 (dd, J=8.4, 0.7 Hz, 1H), 6.97 (d, J=7.5 Hz, 1H), 4.02 (s, 3H), 3.80 (m, 4H), 3.72 (m, 4H); Anal. Calcd. for C22H19F2N9O2: C, 55.1; H, 4.0; N, 26.3. Found: C, 55.3; H, 4.1; N, 26.5.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered through celite
  3. washThe celite plug was washed with CH2Cl2 and CH2Cl2/MeOH (9:1) before the solvents
  4. customwere removed under vacuum
  5. washChromatography on silica, eluting with hexanes/EtOAc (70:30 to 20:80)
  6. customfollowed by recrystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-4accd42b24214bada212cfb27264f9a7
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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