Sodium hydride → HCID 59856811, compound

HRID 1036804Notes

Reaction equation

HRID 1036804 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH:20]3[CH2:22][CH2:21]3)=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[F:24][C:25]1[CH:30]=[C:29]([S:31]([CH3:34])(=[O:33])=[O:32])[CH:28]=[CH:27][C:26]=1[OH:35].[H-].[Na+]>CS(C)=O>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH:20]3[CH2:22][CH2:21]3)=[C:18]([O:35][C:26]3[CH:27]=[CH:28][C:29]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:30][C:25]=3[F:24])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 161288422-Fluoro-4-methylsulfonylphenolHCID 86597367HCID 86597367, compound

Product 1

HCID 59856811HCID 59856811, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

4-(6-Chloro-5-cyclopropyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (200 mg, 0.588 mmol), 2-fluoro-4-methanesulfonyl-phenol (168 mg, 0.883 mmol) and sodium hydride (60% dispersion in mineral oil, 53 mg, 1.325 mmol) were dissolved in DMSO (2 mL) and the mixture stirred under Nitrogen for 10 min at rt. The mixture was then heated under microwave irradiation for 1 h at 150° C. The crude was quenched with water and extracted with EtOAc (3×). The organic layer was concentrated and the residue was purified by HPLC to afford Compound C44 (51 mg, 14.3%) as oil. 1H NMR (CDCl3, 400 MHz) δ 0.90-0.97 (m, 2H), 1.01-1.06 (m, 2H), 1.23-1.27 (d, J=6.06 Hz, 6H), 1.76-1.91 (m, 2H), 1.92-2.02 (m, 2H), 3.08 (s, 3H), 3.46-3.55 (m, 2H), 3.63-3.72 (m, 2H), 4.87-4.98 (m, 1H), 5.32-5.39 (m, 1H), 7.36-7.42 (m, 1H), 7.73-7.80 (m, 2H), 8.17 (s, 1H). Exact mass calculated for C23H28FN3O6S 493.17, found 494.5 (MH+).

Workup

  1. temperatureThe mixture was then heated under microwave irradiation for 1 h at 150° C
  2. customThe crude was quenched with water
  3. extractionextracted with EtOAc (3×)
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified by HPLC
  6. customto afford Compound C44 (51 mg, 14.3%) as oil

Sources & evidence

ORD record
ord-ab26ee4ccf534d58ac14476ffd68fa05
Source dataset
uspto-grants-2013_10
Patent number
US08546429B2

Reaction notes

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