Lithium diisopropylamide → HCID 67432380, compound

HRID 410682Notes

Reaction equation

HRID 410682 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH:7]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH:33]1[CH2:39][CH2:38][CH2:37][CH2:36][N:35]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)[C:34]1=[O:49]>C1COCC1>[CH3:48][O:47][C:44]1[CH:43]=[CH:42][C:41]([CH2:40][N:35]2[CH2:36][CH2:37][CH2:38][CH2:39][CH:33]([C:11]3[S:12][C:8]([C:6]4[CH:5]=[C:4]([NH:13][C:14]5[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=5)[CH:3]=[C:2]([CH3:1])[CH:7]=4)=[CH:9][N:10]=3)[C:34]2=[O:49])=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×HCID 58456423HCID 58456423, compound

Product 1

HCID 67432380HCID 67432380, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 4, 150 mg, 0.446 mmol) in THF (5 ml) at −78° C., was added lithium diisopropylamide (1.8M in tetrahydrofuran, 0.75 ml, 1.350 mmol). The mixture was stirred at −78° C. for 1 h, and 3-bromo-1-(4-methoxybenzyl)azepan-2-one (146 mg, 0.468 mmol) was added. The mixture was stirred at −78° C. for 2 hr, and the reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with brine, dried and concentrated to afford a residue, which was purified by chromatography on silica gel (ethyl acetate/hexanes=3/7) to afford 1-(4-methoxybenzyl)-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-one (134.5 mg, 0.237 mmol, 53.1% yield). ESI: [M+H]+ m/z 568.2.

Workup

  1. stirringThe mixture was stirred at −78° C. for 2 hr
  2. customthe reaction was quenched with saturated aqueous ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customto afford a residue, which
  8. customwas purified by chromatography on silica gel (ethyl acetate/hexanes=3/7)

Sources & evidence

ORD record
ord-fd7b4d01c91a466fbfde244b887d5109
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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