Triethylamine → N1-(2-cyclopentylethyl)-4-methyl-N3-(6-(3-methylbutanamido)pyridin-3-yl)isophthalamide

HRID 453385Notes

Reaction equation

HRID 453385 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:27])[C:10]2[CH:11]=[C:12]([CH:23]=[CH:24][C:25]=2[CH3:26])[C:13]([NH:15][CH2:16][CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:14])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:35](Cl)(=[O:40])[CH2:36][CH:37]([CH3:39])[CH3:38]>O>[CH:18]1([CH2:17][CH2:16][NH:15][C:13](=[O:14])[C:12]2[CH:23]=[CH:24][C:25]([CH3:26])=[C:10]([C:9]([NH:8][C:5]3[CH:6]=[N:7][C:2]([NH:1][C:35](=[O:40])[CH2:36][CH:37]([CH3:39])[CH3:38])=[CH:3][CH:4]=3)=[O:27])[CH:11]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66054Isovaleryl chlorideHCID 24812718N'-(6-aminopyridin-3-yl)-N-(2-cyclopentylethyl)-4-methyl-benzene-1,3-dicarboxamide

Product 1

HCID 59381892N1-(2-cyclopentylethyl)-4-methyl-N3-(6-(3-methylbutanamido)pyridin-3-yl)isophthalamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a 25 mL round-bottomed flask was added N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide (0.19 g, 0.52 mmol) and Triethylamine (0.18 ml, 1.3 mmol) to stir at 0° C. Isovaleryl chloride (0.14 ml, 1.0 mmol) was added to the solution dropwise. The reaction was allowed to stir for one hour. At which time was shown to be at completion by LC/MS. DI water was added to the reaction. The reaction was transferred to a separatory funnel, where the aqueous layer was extracted 3 times with DCM. The combined organic layers were washed with brine, saturated NaHCO3, dried with MgSO4, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (25M), eluting with a gradient of 1% to 10% MeOH in CH2Cl2, to provide N1-(2-cyclopentylethyl)-4-methyl-N3-(6-(3-methylbutanamido)pyridin-3-yl)isophthalamide as a white solid. MS (ESI, pos. ion) m/z: 451.3 (M+1).

Workup

  1. stirringto stir for one hour
  2. customThe reaction was transferred to a separatory funnel
  3. extractionwhere the aqueous layer was extracted 3 times with DCM
  4. washThe combined organic layers were washed with brine, saturated NaHCO3
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed through a Biotage pre-packed silica gel column (25M)
  9. washeluting with a gradient of 1% to 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-e1476b859f6f4f95ac89a43b52a7de9b
Source dataset
uspto-grants-2013_07
Patent number
US08492404B2

Reaction notes

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