N,N-Dimethylglycine → HCID 21941908, compound

HRID 1529579Notes

Reaction equation

HRID 1529579 reaction equation
FC1C=CC(C([N:10]2[CH2:15][CH2:14][C:13]3[N:16]=[C:17](CO)[O:18][C:12]=3[CH2:11]2)=O)=CC=1.BrC1C=C(C)C=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.[Cu](I)I>[N:16]1[C:13]2[CH2:14][CH2:15][NH:10][CH2:11][C:12]=2[O:18][CH:17]=1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 27340872-Bromo-4-methylpyridineHCID 66613314HCID 66613314, compound

Product 1

HCID 21941908HCID 21941908, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Copper iodide (17 mg, 0.09 mmol) was added to a stirred suspension of {5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridin-2-yl}methanol (50 mg, 0.18 mmol), 2-bromo-4-methylpyridine (0.04 mL, 0.36 mmol), cesium carbonate (118 mg, 0.36 mmol) and N,N-dimethylglycine (18 mg, 0.18 mmol) in 1,4-dioxane (1 mL) in a sealed tube and under nitrogen. The mixture was stirred at 120° C. for 60 hours. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7N solution of ammonia in MeOH in DCM 0/100 to 4/96). The desired fractions were collected and the solvents evaporated in vacuo. The crude product was purified by RP HPLC on (C18 XBridge 19×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 100% ACN). The solvents were evaporated in vacuo to yield 5-[(4-fluorophenyl)carbonyl]-2-1[(4-methylpyridin-2-yl)oxy]methyl}-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (6.7 mg, 10% yield) as a colourless oil. C20H18FN3O3 1H NMR (400 MHz, CDCl3) δ ppm 2.30 (s, 3 H), 2.72 (br. s., 2 H), 3.69 (br.s., 2 H), 4.75 (br. s., 2 H), 5.43 (s, 2 H), 6.65 (s, 1 H), 6.75 (d, J=5.1 Hz, 1 H), 7.13 (t, J=8.4 Hz, 2 H), 7.40-7.52 (m, 2 H), 8.01 (d, J=5.1 Hz, 1 H).

Workup

  1. washwashed with a 16% aqueous solution of NH4OH
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; 7N solution of ammonia in MeOH in DCM 0/100 to 4/96)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customThe crude product was purified by RP HPLC on (C18 XBridge 19×100 5 um)
  10. customThe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-e73038e8d6eb493fa08fdf14cbc6c6b5
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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