Diisopropylethylamine → 5-bromo-6-cyclopropylmethoxy-N-(trans-2-hydroxy-cyclohexyl)-nicotinamide

HRID 1159233Notes

Reaction equation

HRID 1159233 reaction equation
[Br:1][C:2]1[C:3]([O:11][CH2:12][CH:13]2[CH2:15][CH2:14]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:47][C@@H:48]1[CH2:53][CH2:52][CH2:51][CH2:50][C@H:49]1[OH:54]>CN(C=O)C>[Br:1][C:2]1[C:3]([O:11][CH2:12][CH:13]2[CH2:15][CH2:14]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:47][C@@H:48]1[CH2:53][CH2:52][CH2:51][CH2:50][C@H:49]1[OH:54])=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 211097085-Bromo-6-(cyclopropylmethoxy)nicotinic acid

Product 1

HCID 675049715-bromo-6-cyclopropylmethoxy-N-(trans-2-hydroxy-cyclohexyl)-nicotinamideYield 79.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-6-cyclopropylmethoxy-nicotinic acid (2.3 g, 8.5 mmol) was dissolved in DMF (75 mL). To the solution was added TBTU (2.99 g, 9.3 mmol), N,N-diisopropylethyl amine (7.2 mL, 42 mmol) and (trans)-2-amino-cyclohexanol (1.4 g, 9.3 mmol). 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 2.5 g of the title compound as a white solid, MS (ISP) 368.9, 371.0 (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-19c2b52f8cda4fb28409dd997b14ed88
Source dataset
uspto-grants-2010_10
Patent number
US07812028B2

Reaction notes

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