Lithium Hexamethyldisilazide → N-{3-[(Z)-2-(2-Chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamide

HRID 590011Notes

Reaction equation

HRID 590011 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=1)[C:16]([O:18]CC)=O)(=[O:11])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:34][C:35]1[N:40]=[C:39]([CH3:41])[CH:38]=[CH:37][N:36]=1>C1COCC1>[Cl:34][C:35]1[N:40]=[C:39](/[CH:41]=[C:16](/[C:15]2[CH:14]=[C:13]([NH:12][S:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])(=[O:11])=[O:10])[CH:23]=[CH:22][CH:21]=2)\[OH:18])[CH:38]=[CH:37][N:36]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 8823788Ethyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}benzoateHCID 116296072-Chloro-4-methylpyrimidine

Product 1

HCID 136176025N-{3-[(Z)-2-(2-Chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamideYield 96.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirring solution of ethyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}benzoate (47.9 g, 140 mmol) in 100 mL anhydrous THF at 0° C. was added 1M LiHMDS in THF (421 mL, 421 mmol). A solution of 2-chloro-4-methylpyrimidine (19.9 g, 154 mmol) in 100 mL of anhydrous THF was added to the reaction mixture over 30 min and warmed to rt. The reaction mixture was quenched with 50 mL of MeOH and concentrated to a black solid under vacuum. The residue was partitioned between DCM and 10% NaHSO4. The aqueous and suspended solids were extracted 2× with DCM and the combined organic extracts were filtered through a pad of Celite, concentrated, and passed through a short silica gel column (elution with THF) to provide 57 g (96%) of the title compound of Step B. 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.03-11.34 (m, 1H), 8.49-8.91 (m, 1H), 7.79 (d, J=7.4 Hz, 1H), 7.65-7.76 (m, 2H), 7.55-7.63 (m, 1H), 7.50 (t, J=7.7 Hz, 1H), 7.35-7.47 (m, 1H), 7.22-7.34 (m, 2H), 6.43 (s, 1H), and 4.60 (s, 1H); ES-LCMS m/z 423.93 (M+H).

Workup

  1. customThe reaction mixture was quenched with 50 mL of MeOH
  2. concentrationconcentrated to a black solid under vacuum
  3. customThe residue was partitioned between DCM and 10% NaHSO4
  4. extractionwere extracted 2× with DCM
  5. filtrationthe combined organic extracts were filtered through a pad of Celite
  6. concentrationconcentrated
  7. washpassed through a short silica gel column (elution with THF)

Sources & evidence

ORD record
ord-2fac74abf54141e0ae7d9dd5c28fcf1f
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

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