Potassium Carbonate → 2-[2-(difluoromethyl)-7-methoxy-2,3-dihydro-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine

HRID 450196Notes

Reaction equation

HRID 450196 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)[C:5]([N+:15]([O-:17])=[O:16])=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:3]=1.[F:24][CH:25]([F:37])[C:26]1[NH:30][C:29]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:28]=2[N:27]=1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl.CCOC(C)=O>CS(C)=O.O>[F:37][CH:25]([F:24])[CH:26]1[N:27]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[N:11][CH:12]=[N:13][CH:14]=3)[C:5]([N+:15]([O-:17])=[O:16])=[C:4]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:3]=2)[C:28]2[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:29]=2[NH:30]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 21226138Dichloromethane ethylacetateHCID 534881012-(Difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 866497822-chloro-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine

Product 1

HCID 668703202-[2-(difluoromethyl)-7-methoxy-2,3-dihydro-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamineYield 86%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 0.465 g (1.38 mmol) of the above nitro compound, 0.368 g (1.86 mmol) of 2-difluoromethyl-4-methoxy-1H-benzimidazole (Example 2) and 0.762 g (5.52 mmol) of powdered K2CO3 in 5 mL of DMSO was heated at 120° C. for 8 hrs. The reaction mixture was diluted with water, and extracted with EtOAc (×4). The organic layer was washed with brine, dried, and concentrated. Chromatography on silica, eluting first with hexanes/EtOAc (7:3) and then with CH2Cl2/EtOAc (1:2), gave 0.592 g (86% yield) of 2-[2-(difluoromethyl)-7-methoxy-2,3-dihydro-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine, as a yellow powder: 1H NMR (CDCl3) δ 10.26 (s, 1H), 9.16 (s, 1H), 8.98 (s, 2H), 7.38 (dd, J=8.4, 0.6 Hz, 1H), 7.20 (t, J=8.4 Hz, 1H), 7.12 (t, JHF=53.5 Hz, 1H), 6.78 (d, J=7.8 Hz, 1H), 4.01 (s, 3H), 3.87 (t, J=4.8 Hz, 4H), 3.70 (t, J=4.8 Hz, 4H).

Workup

  1. extractionextracted with EtOAc (×4)
  2. washThe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. washChromatography on silica, eluting first with hexanes/EtOAc (7:3)

Sources & evidence

ORD record
ord-9aba529e8e2b4a4d8b20a3f12addb50c
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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