Sodium hydride → HCID 44477406, compound

HRID 2361652Notes

Reaction equation

HRID 2361652 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:17][CH:16]([OH:18])[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:22]1[N:27]=[CH:26][C:25]([C:28]([NH:30][CH3:31])=[O:29])=[CH:24][CH:23]=1>CS(C)=O>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:15][CH:16]([O:18][C:22]4[N:27]=[CH:26][C:25]([C:28]([NH:30][CH3:31])=[O:29])=[CH:24][CH:23]=4)[CH2:17]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 123642306-Chloro-N-methylnicotinamideHCID 44462713HCID 44462713, compound

Product 1

HCID 44477406HCID 44477406, compoundYield 135.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of 1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-ol (40 mg, 0.158 mmol) in DMSO (2 ml) was added NaH (14 mg, 0.316 mmol, 60 in mineral oil) at RT in one portion. The suspension was stirred for 2 h at RT then 6-chloro-N-methylpyridine-3-carboxamide (54 mg, 0.316 mmol) was added in one portion. The mixture was heated at 80-100° C. in a sealed tube over night. After cooling to RT, the solution was partitioned between brine/water (1:1 mixture, 15 ml) and DCM (20 ml). The organic layer was separated, washed with brine (2×20 ml), dried (Na2SO4), filtered and concentrated at reduced pressure. The residue was purified by preparative HPLC to provide the title compound as white solid (83 mg, 56% yield).

Workup

  1. temperatureThe mixture was heated at 80-100° C. in a sealed tube over night
  2. temperatureAfter cooling to RT
  3. customthe solution was partitioned between brine/water (1:1 mixture, 15 ml) and DCM (20 ml)
  4. customThe organic layer was separated
  5. washwashed with brine (2×20 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3a94b5bda20d42548052c21197724da5
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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