3-Methoxypropyne → 5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(3-methoxy-prop-1-ynyl)-nicotinamide

HRID 505962Notes

Reaction equation

HRID 505962 reaction equation
[CH2:1]([O:4][CH3:5])[C:2]#[CH:3].Cl[C:7]1[C:22]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)=[CH:21][C:10]([C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[OH:20])=[O:12])=[CH:9][N:8]=1>CN(C)C=O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C:22]2[C:7]([C:3]#[C:2][CH2:1][O:4][CH3:5])=[N:8][CH:9]=[C:10]([CH:21]=2)[C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[OH:20])=[O:12])=[CH:24][CH:25]=1

Participants

5

Reactant 2

HCID 693933-MethoxypropyneHCID 866191846-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide

Product 1

HCID 674260675-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(3-methoxy-prop-1-ynyl)-nicotinamideYield 26%

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Bis(triphenylphosphine)palladium (II) dichloride (52 mg, 0.074 mmol), cuprous (I) iodide (14 mg, 0.074 mmol), triphenylphosphine polystyrene resin(146 mg, 1.48 mmol/g) and propargyl methylether (104 mg, 1.48 mmol) were added under argon at room temperature to a solution of 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide (450 mg, 1.23 mmol) in N,N-dimethylformamide. The mixture was irradiated for 70 min in a microwave oven at 120° C. The polystyrene resin was filtered off and washed with ethylacetate. The filtrate was treated with 1 N HCl (80 mL); phases were separated and the water phase was extracted with ethyl acetate (2×100 mL). The organic phases were washed with water (100 mL) and saturated sodium bicarbonate solution (100 mL). Organic phases were then combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography (heptane/ethyl acetate 1:2 to 1:9) to give 5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(3-methoxy-prop-1-ynyl)-nicotinamide as a light yellow solid; 0.13 g (26% yield). m/z (ISP+): 399.1 (M+H).

Workup

  1. customThe mixture was irradiated for 70 min in a microwave oven at 120° C
  2. filtrationThe polystyrene resin was filtered off
  3. washwashed with ethylacetate
  4. additionThe filtrate was treated with 1 N HCl (80 mL)
  5. customphases were separated
  6. extractionthe water phase was extracted with ethyl acetate (2×100 mL)
  7. washThe organic phases were washed with water (100 mL) and saturated sodium bicarbonate solution (100 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash column chromatography (heptane/ethyl acetate 1:2 to 1:9)

Sources & evidence

ORD record
ord-1658fbca15244203b96c648188286978
Source dataset
uspto-grants-2010_08
Patent number
US07781593B2

Reaction notes

Loading…