Methanol → HCID 58243376, compound

HRID 2361681Notes

Reaction equation

HRID 2361681 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](F)=[CH:24][N:23]=1.[CH3:29][OH:30]>CS(C)=O.ClCCl>[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]([O:30][CH3:29])=[CH:24][N:23]=4)[CH2:17]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 24758Sodium hydride2×HCID 5834662-Chloro-5-fluoropyrimidineHCID 44462713HCID 44462713, compound

Product 1

HCID 58243376HCID 58243376, compoundYield 28.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-ol (50 mg, 0.197 mmol) in DMSO (2 ml) was added NaH (16 mg of a 60% dispersion in mineral oil, 0.40 mmol) at room temperature in one portion. The suspension was stirred for 2 hours at room temperature then 2-chloro-5-fluoro-pyrimidine (26 mg, 0.20 mmol) was added in one portion. The mixture was heated at 60° C. in a sealed tube for 16 hours. After cooling to room temperature the solution was treated with MeOH (8 μl, 0.20 mmol) and NaH (16 mg, 0.40 mmol, 60 in mineral oil) and heated at 60° C. in a sealed tube for 16 hours. After cooling to room temperature the reaction was diluted with dichloromethane (30 ml) and washed twice with saturated NaHCO3 (15 ml), dried (Na2SO4), 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 provide the title compound as colourless oil (20 mg, 28%).

Workup

  1. temperatureThe mixture was heated at 60° C. in a sealed tube for 16 hours
  2. temperatureAfter cooling to room temperature the solution
  3. temperatureheated at 60° C. in a sealed tube for 16 hours
  4. temperatureAfter cooling to room temperature the reaction
  5. washwashed twice with saturated NaHCO3 (15 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customThe residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 90:10:1)

Sources & evidence

ORD record
ord-cc7470d19e3844ca9fae2c712ddafc28
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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