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

HRID 450194Notes

Reaction equation

HRID 450194 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][CH:12]=[CH: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])[C:26]1[N:30]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[N:11][CH:12]=[CH: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:29]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:28]=2[N:27]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 21226138Dichloromethane ethylacetateHCID 534881012-(Difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 866497812-chloro-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamine

Product 1

HCID 668535842-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamineYield 75%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 0.23 g of the above nitro compound (0.68 mmol), 0.147 g (0.74 mmol) of 2-difluoromethyl-4-methoxy-1H-benzimidazole (Example 2) and 0.38 g (2.75 mmol) of powdered K2CO3 in 4 mL of DMSO was heated at 120° C. for 4 hrs. The reaction mixture was diluted with water, and extracted with EtOAc (×4). The combined organic layers were washed with brine, dried, and concentrated. The residue was purified by chromatography on silica, eluting first with hexanes/EtOAc (1:1), and then with CH2Cl2/EtOAc (2:1), to give 0.253 g (75% yield) of 2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamine, as a yellow powder: 1H NMR (CDCl3) δ 10.26 (s, 1H), 8.72 (d, J=2.4 Hz, 1H), 8.60 (dd, J=4.8, 1.4 Hz, 1H), 7.95 (ddd, J=8.3, 2.4, 1.6 Hz, 1H), 7.45 (dd, J=8.3, 0.6 Hz, 1H), 7.40 (dd, J=8.3, 4.8 Hz, 1H), 7.18 (t, J=8.3 Hz, 1H), 7.11 (t, JHF=53.5 Hz, 1H), 6.78 (d, J=7.8 Hz, 1H), 4.03 (s, 3H), 3.88 (t, J=4.5 Hz, 4H), 3.70 (t, J=4.5 Hz, 4H).

Workup

  1. extractionextracted with EtOAc (×4)
  2. washThe combined organic layers were washed with brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica
  6. washeluting first with hexanes/EtOAc (1:1)

Sources & evidence

ORD record
ord-bbef3ee995114e8892fd80918f18ad52
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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