Methanesulfonyl chloride → HCID 57818414, compound

HRID 705585Notes

Reaction equation

HRID 705585 reaction equation
[F:1][C:2]1[C:3]([NH2:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C1COCC1>[F:1][C:2]1[C:3]([NH:17][S:29]([CH3:28])(=[O:31])=[O:30])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 50991248HCID 50991248, compound

Product 1

HCID 57818414HCID 57818414, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-ylamine (0.100 g, 0.43 mmol) in anhydrous THF (4 mL) was added LiHMDS (1.07 mL of 1.0M, 1.07 mmol) dropwise at room temperature, and the resulting orange solution was stirred for 20 min. Methanesulfonyl chloride (0.108 g, 0.94 mmol) was added in one portion and the turbid, light orange solution was stirred for 60 min. The reaction was quenched with brine (5 mL) and the THF phase was separated. The aq. phase was extracted w/ EtOAc (5 mL), and the organics were combined, dried over Na2SO4, filtered, and concentrated to an orange gummy residue. The residue was purified by flash chromatography (SiO2, 0→100% EtOac/hexanes) to give 0.034 g (26%) of the title compound as a white solid: mp 145-148° C.; 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.33 (d, J=7.9 Hz, 2H), 7.17 (d, J=7.9 Hz, 2H), 5.35 (s, 2H), 3.37 (s, 3H), 2.35 (s, 3H); HPLC-MS (ESI) m/z 312 (M+H)+, 310 (M−H)−.

Workup

  1. stirringthe turbid, light orange solution was stirred for 60 min
  2. customThe reaction was quenched with brine (5 mL)
  3. customthe THF phase was separated
  4. extractionThe aq. phase was extracted w/ EtOAc (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to an orange gummy residue
  8. customThe residue was purified by flash chromatography (SiO2, 0→100% EtOac/hexanes)

Sources & evidence

ORD record
ord-6a2f15b19fdf4a55ab11912cd5bddb2c
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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