Lithium diisopropylamide → 2-methyl-N-{3-[5-(3-methyl-5-[[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl]propane-2-sulfinamide

HRID 410575Notes

Reaction equation

HRID 410575 reaction equation
C(NC(C)C)(C)C.[Li].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[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.[Li+].CC([N-]C(C)C)C.[CH3:40][C:41]([S:44]([N:46]=[C:47]1[CH2:50][O:49][CH2:48]1)=[O:45])([CH3:43])[CH3:42]>C1COCC1>[CH3:43][C:41]([S:44]([NH:46][C:47]1([C:19]2[S:20][C:16]([C:14]3[CH:13]=[C:12]([NH:21][C:22]4[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=4)[CH:11]=[C:10]([CH3:9])[CH:15]=3)=[CH:17][N:18]=2)[CH2:50][O:49][CH2:48]1)=[O:45])([CH3:40])[CH3:42]

Participants

6

Reactant 4

HCID 2724682Lithium diisopropylamideHCID 45051747Lithium diisopropylamineHCID 468399952-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×

Product 1

HCID 672573262-methyl-N-{3-[5-(3-methyl-5-[[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl]propane-2-sulfinamideYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of lithium diisopropylamine (1.8 M, 4.96 mL, 8.92 mmol) in THF (8 mL) was placed under an Argon atmosphere and was cooled to −78° C. A solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (Intermediate 4, 1200 mg, 3.57 mmol) in THF (8 mL) was cooled to −78° C. and added drop wise to the LDA solution. The reaction mixture was stirred 30 minutes at −78° C. The product of Step 1 (625 mg, 3.57 mmol) in THF (8 mL) was added drop wise and the reaction was allowed to warm to room temperature overnight. The mixture was quenched with brine, diluted with ethyl acetate. The organics were washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (20-100% ethyl acetate in hexanes) to afford 2-methyl-N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}propane-2-sulfinamide (1.10 g, 2.140 mmol, 60.0% yield). MS ESI: [M+H]+ m/z 512.1.

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe mixture was quenched with brine
  3. additiondiluted with ethyl acetate
  4. washThe organics were washed with saturated NaHCO3
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica (20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e3e013da18414981b10036bbf45efa41
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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