Diisopropylethylamine → 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide

HRID 505961Notes

Reaction equation

HRID 505961 reaction equation
[Cl:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.Cl.[NH2:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]1[OH:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C>CN(C)C=O>[Cl:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:9][C:5]([C:6]([NH:19][C@@H:20]2[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]2[OH:26])=[O:8])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 866191836-Chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid

Product 1

HCID 866191846-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamideYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Chloro-5-(4-chloro-phenyl)-nicotinic acid (1.4 g, 5 mmol) was dissolved in N,N-dimethylformamide (30 mL). To this solution was added sequentially (1R,2R)-2-amino-cyclohexanol hydrochloride (0.87 g, 6 mmol), TBTU (1.84 g, 6 mmol), and N-ethyldiisopropylamine (4.47 mL, 26 mmol). The reaction mixture was stirred at room temperature for 72 hours then concentrated in vacuo. The residue was then dissolved in ethyl acetate (100 mL) and washed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL). The aqueous phases were extracted with ethyl acetate (2×100 mL), the organics were combined and the whole was dried over MgSO4 and concentrated in vacuo. The solid residue was purified by stirring with (ethylacetate/heptane 1:2, 50 mL) to give 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide as a colorless solid, 1.4 g (73% yield). m/z (ISP+): 364.9, 366.9 (M+H).

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was then dissolved in ethyl acetate (100 mL)
  3. washwashed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL)
  4. extractionThe aqueous phases were extracted with ethyl acetate (2×100 mL)
  5. dry with materialthe whole was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe solid residue was purified
  8. stirringby stirring with (ethylacetate/heptane 1:2, 50 mL)

Sources & evidence

ORD record
ord-257f3894c5a64ad1a8c9787558b1f0ef
Source dataset
uspto-grants-2010_08
Patent number
US07781593B2

Reaction notes

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