1-Hydroxybenzotriazole → HCID 86716211, compound

HRID 512183Notes

Reaction equation

HRID 512183 reaction equation
[F:1][C:2]1([F:18])[CH2:7][CH2:6][C:5]([C:11]2[CH:12]=[N:13][C:14]([CH3:17])=[N:15][CH:16]=2)([C:8]([OH:10])=O)[CH2:4][CH2:3]1.Cl.[CH3:20][NH:21][O:22][CH3:23].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:18][C:2]1([F:1])[CH2:3][CH2:4][C:5]([C:11]2[CH:12]=[N:13][C:14]([CH3:17])=[N:15][CH:16]=2)([C:8]([N:21]([O:22][CH3:23])[CH3:20])=[O:10])[CH2:6][CH2:7]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86716209HCID 86716209, compound

Product 1

HCID 86716211HCID 86716211, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4,4-difluoro-1-(2-methylpyrimidin-5-yl)cyclohexanecarboxylic acid (1.2 g, 4.68 mmol), N,O-dimethylhydroxylamine hydrochloride (456 mg, 4.68 mmol), HOBt (759.33 mg, 5.62 mmol), EDCI.HCl (1.08 g, 5.62 mmol) and DIPEA (3.23 mL, 18.73 mmol) in DMF (20 mL) was stirred at room temperature. The reaction mixture was added water and extracted with EtOAc (3×50 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated to give 4,4-difluoro-N-methoxy-N-methyl-1-(2-methylpyrimidin-5-yl)cyclohexanecarboxamide (380 mg), which was used for the next step directly. About 0.9 g of 4,4-difluoro-1-(2-methylpyrimidin-5-yl)cyclohexanecarboxylic acid was recycled.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7b7367e391714731a98b90612f0c1b20
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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