Sodium hydride → HCID 58243405, compound

HRID 2361690Notes

Reaction equation

HRID 2361690 reaction equation
[F-].[K+].C1N2CCOCCOCCN(CCOCCOCC2)CCOCCOC1.Cl[C:30]1[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[C:31]=1[F:37].[H-].[Na+].[CH:40]1([N:44]2[CH2:50][CH2:49][CH2:48][N:47]([C:51]([N:53]3[CH2:56][CH:55]([OH:57])[CH2:54]3)=[O:52])[CH2:46][CH2:45]2)[CH2:43][CH2:42][CH2:41]1>CS(C)=O.CCOC(C)=O>[CH:40]1([N:44]2[CH2:50][CH2:49][CH2:48][N:47]([C:51]([N:53]3[CH2:54][CH:55]([O:57][C:30]4[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[C:31]=4[F:37])[CH2:56]3)=[O:52])[CH2:46][CH2:45]2)[CH2:43][CH2:42][CH2:41]1

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 728012,2,2-CryptandHCID 522689Potassium FluorideHCID 187277504-Chloro-3-fluoro-2-methylpyridineHCID 44462713HCID 44462713, compound

Product 1

HCID 58243405HCID 58243405, compoundYield 35.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

KF (73 mg, 1.25 mmol) was dried under vacuum for 2 hours and then stirred with Kryptofix-222 (282 mg, 0.75 mmol) and 4-chloro-3-fluoro-2-methylpyridine (40 mg, 0.28 mmol) in DMSO (3 ml) at 120° C. for 16 hours in a sealed tube. After cooling to room temperature, NaH (100 mg of a 60% dispersion in mineral oil, 2.5 mmol) and 1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-ol (63 mg, 0.25 mmol) were added and stirred for a further 8 hours. The reaction was diluted with EtOAc (30 ml) and washed with saturated NaHCO3 (3×15 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 90:10:1) to give the title compound (32 mg, 35%) as yellow oil.

Workup

  1. washwashed with saturated NaHCO3 (3×15 ml)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 90:10:1)

Sources & evidence

ORD record
ord-52c0ba105904454fbdee995a593dea68
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

Loading…