4-Fluorobenzylamine → 4-(3-chloro-4-methoxybenzyloxy)-2-(methylmercapto)-N-(4-fluorobenzyl)pyrimidine-5-carboxamide

HRID 874513Notes

Reaction equation

HRID 874513 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:5][O:6][C:7]1[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]([S:16][CH3:17])[N:8]=1.[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:5][O:6][C:7]1[C:12]([C:13]([NH:29][CH2:28][C:27]2[CH:30]=[CH:31][C:24]([F:23])=[CH:25][CH:26]=2)=[O:15])=[CH:11][N:10]=[C:9]([S:16][CH3:17])[N:8]=1

Participants

7

Reactant 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712350394-(3-chloro-4-methoxybenzyloxy)-2-(methylmercapto)pyrimidine-5-carboxylic Acid

Product 1

HCID 901694574-(3-chloro-4-methoxybenzyloxy)-2-(methylmercapto)-N-(4-fluorobenzyl)pyrimidine-5-carboxamideYield 52.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(3-chloro-4-methoxybenzyloxy)-2-(methylmercapto)pyrimidine-5-carboxylic acid (300 mg, 0.88 mmol) and 4-fluorobenzylamine (165 mg, 1.32 mmol) were dissolved in 20 mL THF, DIEA (0.45 mL, 2.64 mmol) was added dropwise, HATU (401 mg, 1.06 mmol) was added under ice-water-bath, reacted at room temperature for 4 h, to the reaction solution was added 100 mL of water, then extracted with dichloromethane, dried with anhydrous sodium sulfate, dried by rotation, the solid was separated with silica gel separation (dichloromethane:methanol=100:1) to obtain a white solid 4-(3-chloro-4-methoxybenzyloxy)-2-(methylmercapto)-N-(4-fluorobenzyl)pyrimidine-5-carboxamide 206 mg, yield 52%.

Workup

  1. customreacted at room temperature for 4 h, to the reaction solution
  2. extractionextracted with dichloromethane
  3. dry with materialdried with anhydrous sodium sulfate
  4. customdried by rotation
  5. customthe solid was separated with silica gel separation (dichloromethane:methanol=100:1)

Sources & evidence

ORD record
ord-3378e5d8212b46b7a99baa70c31bda75
Source dataset
uspto-grants-2015_03
Patent number
US08980904B2

Reaction notes

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