Diisopropylethylamine → N1-(2-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-(piperidin-1-yl)-phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide

HRID 1408060Notes

Reaction equation

HRID 1408060 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[CH:23]=[CH:22][C:20]=3[NH2:21])[CH:14]=2)[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][N:33]([CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1)[C:34]([C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=1)[C:39](O)=[O:40])=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[CH:23]=[CH:22][C:20]=3[NH:21][C:39](=[O:40])[C:38]3[CH:42]=[CH:43][CH:44]=[C:36]([C:34]([N:33]([CH3:32])[CH2:45][CH2:46][N:47]4[CH2:48][CH2:49][O:50][CH2:51][CH2:52]4)=[O:35])[CH:37]=3)[CH:14]=2)[N:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665869413-(Methyl(2-morpholinoethyl)carbamoyl)benzoic acidHCID 665875432-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-(piperidin-1-yl)aniline

Product 1

HCID 86705947N1-(2-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-(piperidin-1-yl)-phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamideYield 37.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 22 mg of 2-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-(piperidin-1-yl)aniline 24d, 15.2 mg of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoic acid, 22.6 mg of HATU, and 27.9 mg of diisopropylethylamine in 0.3 mL of DMF was stirred for 1 h. The solution was filtered and the product was isolated from the filtrate by reverse phase chromatography eluting with 0.05% TFA in a water/acetonitrile gradient. This procedure gave 13.4 mg of product. 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.97 (s, 1H), 8.78 (d, J=5.0 Hz, 1H), 8.35 (s, 1H), 8.32-8.26 (m, 1H), 8.03-7.94 (m, 2H), 7.91 (d, J=5.2 Hz, 1H), 7.70-7.50 (m, 3H), 7.35 (mj, 4H), 7.28-7.19 (m, 1H), 5.69 (s, 2H), 4.09-3.90 (m, 3H), 3.85-3.76 (m, 2H), 3.71-3.53 (m, 4H), 2.91 (s, 3H), 1.69 (s, 4H), 1.55 (s, 2H). MS (ESI, m/z) 685.3 [M+H]+.

Workup

  1. filtrationThe solution was filtered
  2. customthe product was isolated from the filtrate by reverse phase chromatography
  3. washeluting with 0.05% TFA in a water/acetonitrile gradient

Sources & evidence

ORD record
ord-c71fc2be68bf486680287bee6df4d7c2
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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