Acetic Acid → 6-[4-(Methylsulfonyl)phenyl]-5-phenyl-4-[4-(1,3-thiazol-2-yl methyl)piperazin-1-yl]-2-(trifluoromethyl)pyrimidine

HRID 72670Notes

Reaction equation

HRID 72670 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:14]=[C:13]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:12]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[S:33]1[CH:37]=[CH:36][N:35]=[C:34]1[CH:38]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C.C(OCC)(=O)C.O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:14]=[C:13]([N:21]3[CH2:22][CH2:23][N:24]([CH2:38][C:34]4[S:33][CH:37]=[CH:36][N:35]=4)[CH2:25][CH2:26]3)[C:12]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 27349031,3-Thiazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 580894536-[4-(Methylsulfonyl)phenyl]-5-phenyl-4-piperazin-1-yl-2-(trifluoromethyl)pyrimidine

Product 1

HCID 249586646-[4-(Methylsulfonyl)phenyl]-5-phenyl-4-[4-(1,3-thiazol-2-yl methyl)piperazin-1-yl]-2-(trifluoromethyl)pyrimidineYield 45.6%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
37 °C

Procedure

To a solution of 6-[4-(methylsulfonyl)phenyl]-5-phenyl-4-piperazin-1-yl-2-(trifluoromethyl)pyrimidine (0.2 g, 0.43 mmol, prepared according to the procedure described in preparation 2) in dichloroethane (25 ml) was added thiazole-2-carboxaldehyde (0.144 g, 1.3 mmol) under stirring at 37° C. After five minutes, sodium triacetoxy borohydride (0.364 g, 1.72 mmol) was added to reaction mixture and then after 10 minutes, acetic acid (0.1 ml) was added to it. The reaction mixture was stirred for 36 hours under the same conditions. Subsequently the reaction mixture was treated with ethyl acetate:water (1:1, 100 ml) and extracted with ethyl acetate (3×50 ml). The organic layer was washed with brine (100 ml) and dried over anhydrous sodium sulphate. The solid obtained upon evaporation was purified by column chromatography using methanol: dichloromethane (0.5:99.5) as an eluent to afford the title compound (0.11 g, yield 45.6%). 1H-NMR (CDCl3) δ: 0.88-0.89 (m, 2H), 1.25-1.28 (t, 2H), 1.33-1.38 (t, 2H), 2.85 (s, 6H), 2.97 (s, 3H), 7.04-7.74 (m, 9H); MS m/z: 544.59 (M++1).

Workup

  1. waitafter 10 minutes
  2. stirringThe reaction mixture was stirred for 36 hours under the same conditions
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. washThe organic layer was washed with brine (100 ml)
  5. dry with materialdried over anhydrous sodium sulphate
  6. customThe solid obtained upon evaporation
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-6b2242c8195d414b9669dff37670579b
Source dataset
uspto-grants-2014_09
Patent number
US08828999B2

Reaction notes

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