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

HRID 1929800Notes

Reaction equation

HRID 1929800 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][CH:19]3[CH2:21][CH2:20]3)=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([OH:15])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:53][C@@H:54]1[CH2:59][CH2:58][CH2:57][CH2:56][C@H:55]1[OH:60]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([O:17][CH2:18][CH:19]3[CH2:21][CH2:20]3)=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([NH:53][C@@H:54]2[CH2:59][CH2:58][CH2:57][CH2:56][C@H:55]2[OH:60])=[O:15])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 666874825-(4-Chlorophenyl)-6-(cyclopropylmethoxy)nicotinic acid

Product 1

HCID 119511245-(4-Chloro-phenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamideYield 76.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(4-Chloro-phenyl)-6-cyclopropylmethoxy-nicotinic acid (21.5 g, 0.071 mol) was dissolved in DMF (655 mL). To the solution was added TBTU (25 g, 0.078 mol), N,N-diisopropylethyl amine (60.5 mL, 0.35 mol) and (1R,2R)-2-amino-cyclohexanol (11.8 g, 0.078 mol). The reaction mixture was stirred for 16 h at room temperature. The solvent was evaporated in vacuo and the residue was purified by column chromatography on silica (n-heptane/ethyl acetate gradient) to yield 21.7 g of the title compound as a white solid, MS (ISP) 401.2 (M+H)+.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by column chromatography on silica (n-heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-51597620eccf451ca6207648276a4981
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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