Lithium diisopropylamide → 1-(5-Bromopyridin-2-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyridin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol

HRID 410692Notes

Reaction equation

HRID 410692 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2N=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[Br:32][C:33]1[CH:34]=[CH:35][C:36]([C:39](=[O:41])[CH3:40])=[N:37][CH:38]=1>C1COCC1>[Br:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([C:19]2[S:20][C:16]([C:14]3[CH:13]=[C:12]([NH:21][C:22]4[CH:1]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][N:23]=4)[CH:11]=[C:10]([CH3:9])[CH:15]=3)=[CH:17][N:18]=2)([OH:41])[CH3:40])=[N:37][CH:38]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 231453451-(5-Bromopyridin-2-yl)ethan-1-oneHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×

Product 1

HCID 674303841-(5-Bromopyridin-2-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyridin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanolYield 50.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

THF (20 ml) was cooled to −78° C., and lithium diisopropylamide (7.64 ml, 13.75 mmol) was added. N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 4, 1.85 g, 5.50 mmol) in THF (15 ml) was added drop wise, and the reaction was stirred at −78° C. for 30 min. 1-(5-Bromopyridin-2-yl)ethanone (1.100 g, 5.50 mmol) in THF (5 ml) was subsequently added in one portion. The reaction was stirred for 10 min at −78° C. The dry ice bath was removed, and the reaction was allowed to warm to room temperature. The dark brown reaction mixture was quenched with aqueous saturated NH4Cl solution and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Chromatography on silica gel (Biotage 100 g SNAP, 0-20% EtOAc/toluene) afforded 1-(5-bromopyridin-2-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyridin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (1.487 g, 2.77 mmol, 50.4% yield) as a yellow solid. MS ESI: [M+H]+ m/z 538.0.

Workup

  1. stirringThe reaction was stirred for 10 min at −78° C
  2. customThe dry ice bath was removed
  3. temperatureto warm to room temperature
  4. customThe dark brown reaction mixture was quenched with aqueous saturated NH4Cl solution
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-fe5fab70eaef4509a3b29dc0c3657246
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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