Stannous chloride dihydrate → 4-[5-(Acetylamino)pyridin-2-yl]piperazin-1-yl-5-(4-fluoro phenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine

HRID 1966347Notes

Reaction equation

HRID 1966347 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[C:6]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[N:5]=[C:4]([C:25]([F:28])([F:27])[F:26])[N:3]=1.[N+:29]([C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[N:36][CH:37]=1)([O-])=O.C(N([CH:50]([CH3:52])C)CC)(C)C.[OH2:53].O.[Sn](Cl)Cl>C(O)(=O)C.C(#N)C>[C:50]([NH:29][C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:2]3[C:7]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)=[C:6]([C:15]4[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:22])=[O:23])=[CH:17][CH:16]=4)[N:5]=[C:4]([C:25]([F:27])([F:28])[F:26])[N:3]=3)[CH2:40][CH2:39]2)=[N:36][CH:37]=1)(=[O:53])[CH3:52]

Participants

7

Reactant 4

HCID 61436Stannous chloride dihydrateHCID 81531DiisopropylethylamineHCID 29287991-(5-Nitropyridin-2-yl)piperazineHCID 99105864-Chloro-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoro methyl)pyrimidine

Product 1

HCID 250043724-[5-(Acetylamino)pyridin-2-yl]piperazin-1-yl-5-(4-fluoro phenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
62.5 °C

Procedure

4-Chloro-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoro methyl)pyrimidine (0.15 g, 0.35 mmol) was treated with 1-(5-nitropyridin-2-yl)piperazine (0.087 g, 0.418 mmol) and diisopropylethylamine (0.06 mL, 0.35 mmol), acetonitrile (2.5 ml) and the reaction mixture was heated at 60-65° C. for 2 hours. Subsequently the reaction mixture was precipitated by the addition, of diisopropyl ether (2 ml). The above-obtained solid (0.11 g, 0.182 mmol) was taken up in acetic acid (2 ml) and tin (II) chloride dihydrate (0.123 g, 0.182 mmol) was added to it. Stirring was continued further for 11 hours and then the reaction mixture was poured onto ice-cold water and extracted with ethyl acetate (2×25 ml). After neutralization with sodium bicarbonate, the organic layer was evaporated to obtain the crude material, which was purified by column chromatography (2% MeOH in dichloromethane) to yield the title compound. 1H-NMR (DMSO-d6) δ: 1.99 (s, 3H), 3.19 (s, 3H), 3.29-3.40 (m, 8H), 6.77 (d, 1H), 7.19-7.23 (m, 2H), 7.31-7.34 (m, 2H), 7.36 (d, 2H), 7.74 (d, 1H), 7.80 (d, 2H), 8.24 (d, 1H), 9.77 (s, 1H, D2O exchangeable); MS m/z: 615.1 (M++1).

Workup

  1. customSubsequently the reaction mixture was precipitated by the addition, of diisopropyl ether (2 ml)
  2. additionthe reaction mixture was poured onto ice-cold water
  3. extractionextracted with ethyl acetate (2×25 ml)
  4. customAfter neutralization with sodium bicarbonate, the organic layer was evaporated
  5. customto obtain the crude material, which
  6. customwas purified by column chromatography (2% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-53847db4b281415e8d5e47ce95e97be8
Source dataset
uspto-grants-2013_04
Patent number
US08420653B2

Reaction notes

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