Diisopropylethylamine → 6-{5-[(4,4-Difluorocyclohexylamino)methyl]naphthalen-1-yloxy}-nicotinamide

HRID 2060903Notes

Reaction equation

HRID 2060903 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[C:8]2[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=1)=O.[Cl-].[F:24][C:25]1([F:32])[CH2:30][CH2:29][CH:28]([NH3+:31])[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.[BH4-].[Na+]>CO.O>[F:24][C:25]1([F:32])[CH2:30][CH2:29][CH:28]([NH:31][CH2:1][C:3]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:4]=2[CH:5]=[CH:6][CH:7]=[C:8]3[O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=2)[CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 594013266-(5-Formylnaphthalen-1-yloxy)nicotinamideHCID 178479573HCID 178479573, compound

Product 1

HCID 251221916-{5-[(4,4-Difluorocyclohexylamino)methyl]naphthalen-1-yloxy}-nicotinamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 6-(5-formylnaphthalen-1-yloxy)nicotinamide (Preparation 35) (200 mg, 0.7 mmol) in MeOH (10 mL) was added 4,4-difluorocyclohexylammonium chloride (141 mg, 0.8 mmol), DIPEA (358 μl, 2.1 mmol) and 4 Å molecular sieves (200 mg). The mixture was stirred at 50° C. for 16 h, cooled to rt and NaBH4 (78 mg, 2.1 mmol) added. After 3 h water (1 mL) was added and the mixture filtered. Solvent was removed in vacuo and the residue purified by column chromatography (10% MeOH-EtOAc) to give the title compound: RT=2.40 min; m/z (ES+)=412.2 [M+H]+.

Workup

  1. temperaturecooled to rt
  2. filtrationthe mixture filtered
  3. customSolvent was removed in vacuo
  4. customthe residue purified by column chromatography (10% MeOH-EtOAc)

Sources & evidence

ORD record
ord-b1311cd115ea46428ddebffcf8b2b63d
Source dataset
uspto-grants-2012_10
Patent number
US08278442B2

Reaction notes

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