4-Methoxybenzylamine → HCID 118598764, compound

HRID 1050401Notes

Reaction equation

HRID 1050401 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[C:14](=[O:15])[N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:12]([C:25](O)=[O:26])=[C:11]([Cl:28])[CH:10]=2)[CH:3]=1.[CH3:29][O:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O.O1CCCC1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[C:14](=[O:15])[N:13]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)[C:12]([C:25]([NH:36][CH2:35][C:34]3[CH:37]=[CH:38][C:31]([O:30][CH3:29])=[CH:32][CH:33]=3)=[O:26])=[C:11]([Cl:28])[CH:10]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118598989HCID 118598989, compound

Product 1

HCID 118598764HCID 118598764, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-((6-aminopyrimidin-4-yl)amino)-3-chloro-1-(4-methoxybenzyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid (5, 0.40 g, 0.99 mmol) and 4-methoxybenzylamine (0.16 g, 1.19 mmol) in dimethylformamide (20 mL) was added N,N-diisopropylethylamine (0.39 g, 2.99 mmol) and HATU (0.57 g, 1.99 mmol) at room temperature. The reaction mixture was stirred for 40 h. Progress of the reaction was monitored by LCMS. To the reaction mixture was added tetrahydrofuran (20 mL) and the reaction was refluxed for 7 h. After completion, the reaction was diluted with water (20 mL) and extracted with 10% methanol in dichloromethane (2×30 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure to obtain the crude. The crude was purified by flash column chromatography eluting at 1% methanol in dichloromethane. The best fractions were concentrated to afford 5-((6-aminopyrimidin-4-yl)amino)-3-chloro-N,1-bis(4-methoxybenzyl)-6-oxo-1,6-dihydropyridine-2-carboxamide (6) as yellow solid. Yield: 0.44 g, 84%; MS (ESI) m/z 521.16 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.35 (m, 1H), 8.74 (s, 1H), 8.53 (s, 1H), 8.17 (s, 1H), 7.19-7.16 (m, 4H), 6.87-6.80 (m, 4H), 6.53 (s, 2H), 6.17 (s, 1H), 5.07 (s, 2H), 4.34 (s, 2H), 3.73 (s, 6H).

Workup

  1. temperaturethe reaction was refluxed for 7 h
  2. extractionextracted with 10% methanol in dichloromethane (2×30 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto obtain the crude
  7. customThe crude was purified by flash column chromatography
  8. washeluting at 1% methanol in dichloromethane
  9. concentrationThe best fractions were concentrated

Sources & evidence

ORD record
ord-79d518c23f0a44d29bd9d2c13bd010cc
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

Loading…