Dimethyl Sulfoxide → 4-Nitro-6-{2-[4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethoxy}-pyrimidin-5-ylamine

HRID 1255910Notes

Reaction equation

HRID 1255910 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][OH:18])=[CH:12][CH:11]=2)[CH:4]=1.[H-].[Na+].[NH2:23][C:24]1[C:29]([N+:30]([O-])=O)=[C:28](Cl)[N:27]=[CH:26][N:25]=1.[OH2:34].CS(C)=[O:37]>>[N+:23]([C:24]1[C:29]([NH2:30])=[C:28]([O:18][CH2:17][CH2:16][C:13]2[CH:12]=[CH:11][C:10]([O:9][C:5]3[CH:4]=[C:3]([C:2]([F:19])([F:1])[F:20])[CH:8]=[CH:7][N:6]=3)=[CH:15][CH:14]=2)[N:27]=[CH:26][N:25]=1)([O-:37])=[O:34]

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 24758Sodium hydrideHCID 1012294-Pyrimidinamine, 6-chloro-5-nitro-HCID 581742462-[4-(4-Trifluoromethylpyridin-2-yloxy)-phenyl]-ethanol

Product 1

HCID 670319694-Nitro-6-{2-[4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethoxy}-pyrimidin-5-ylamine

Conditions

Temperature
55 °C

Procedure

2-[4-(4-Trifluoromethylpyridin-2-yloxy)-phenyl]-ethanol (product from Step 1; 400 mg, 1.4 mmol) was dissolved in DMSO (10 mL), treated with 95% NaH (36 mg, 1.5 mmol) and the mixture was warmed to 50-60° C. to produce a clear solution. Upon cooling the mixture was treated with 4-amino-5-nitro-6-chloropyrimidine (260 mg, 1.5 mmol) and heated at 45° C. for 6 h. After cooling the mixture was poured into H2O (60 mL) and the precipitate was collected by suction filtration, washed with H2O and air-dried on the filter: 1H NMR (300 MHz, CDCl3) δ 8.39 (s, 1H), 8.33 (s, 1H), 8.18 (s, 1H), 7.38 (m, 2H), 7.15 (m, 4H), 4.69 (t, J=6.8 Hz, 2H), 3.15 (t, 6.6 Hz, 2H). This material was used in the next step without further purification.

Workup

  1. customto produce a clear solution
  2. temperatureUpon cooling the mixture
  3. temperatureheated at 45° C. for 6 h
  4. temperatureAfter cooling the mixture
  5. filtrationthe precipitate was collected by suction filtration
  6. washwashed with H2O
  7. customair-dried on the
  8. filtrationfilter
  9. customThis material was used in the next step without further purification

Sources & evidence

ORD record
ord-bb9776b318fd4d1bbdeca766bb58615e
Source dataset
uspto-grants-2013_06
Patent number
US08461164B2

Reaction notes

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