Dimethylformamide → N2-Methyl-N2-(2-morpholinoethyl)-N6-(4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)pyridine-2,6-dicarboxamide

HRID 1408017Notes

Reaction equation

HRID 1408017 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][NH:7][C:8](=[O:28])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH2:27])[CH:10]=1.[N:34]1[C:39]([C:40]([OH:42])=O)=[CH:38][CH:37]=[CH:36][C:35]=1[C:43]([OH:45])=O.[CH:46]([N:49]([CH:52]([CH3:54])C)[CH2:50][CH3:51])(C)[CH3:47].[CH3:55][N:56](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=[O:83])C>>[CH3:55][N:56]([CH2:47][CH2:46][N:49]1[CH2:52][CH2:54][O:83][CH2:51][CH2:50]1)[C:40]([C:39]1[CH:38]=[CH:37][CH:36]=[C:35]([C:43]([NH:27][C:16]2[CH:17]=[CH:18][C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:20][C:15]=2[C:11]2[CH:10]=[C:9]([C:8](=[O:28])[NH:7][CH2:6][C:5]3[CH:29]=[CH:30][CH:31]=[C:3]([C:2]([F:1])([F:32])[F:33])[CH:4]=3)[CH:14]=[CH:13][N:12]=2)=[O:45])[N:34]=1)=[O:42]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 103672,6-Pyridinedicarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66586742N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(piperidin-1-yl)phenyl)isonicotinamide

Product 1

HCID 86705943N2-Methyl-N2-(2-morpholinoethyl)-N6-(4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)pyridine-2,6-dicarboxamide

Procedure

A solution of 25 mg of N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(piperidin-1-yl)phenyl)isonicotinamide 4.1c, 28 mg of pyridine-2,6-dicarboxylic acid, and 4.3 mg of diisopropylethylamine in 1 mL of DMF was treated with 21 mg of HATU. After 2 h the mixture was separated by reverse phase HPLC, eluting with 0.05% TFA in a water/acetonitrile gradient. The isolated monoamide adduct of pyridine-2,6-dicarboxylic acid and 4.1c was dissolved in 2 mL of DMF and treated with 10 mg of N-methyl-2-morpholinoethanamine, 28 mg of diisopropylethylamine, and 23 mg of HATU. After 2 h the product was isolated by reverse phase HPLC. MS (ES, m/z) 730 [M+H]+

Workup

  1. customAfter 2 h the mixture was separated by reverse phase HPLC
  2. washeluting with 0.05% TFA in a water/acetonitrile gradient
  3. dissolutionThe isolated monoamide adduct of pyridine-2,6-dicarboxylic acid and 4.1c was dissolved in 2 mL of DMF
  4. additiontreated with 10 mg of N-methyl-2-morpholinoethanamine, 28 mg of diisopropylethylamine, and 23 mg of HATU
  5. customAfter 2 h the product was isolated by reverse phase HPLC

Sources & evidence

ORD record
ord-674807ce52eb42dd8e8b4b13563be8ef
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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