Water → HCID 70978720, compound

HRID 572682Notes

Reaction equation

HRID 572682 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([CH3:10])[N:7]=[C:6]([C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([O:22][CH3:23])[CH:16]=2)=[O:12])[CH:5]=1)(=[O:3])[CH3:2].[CH:24](=O)[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=1.[Cl-].[Al+3].[Cl-].[Cl-].O>C(Cl)Cl>[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][NH:13][C:11]([C:6]2[CH:5]=[C:4]([C:1](=[O:3])[CH:2]=[CH:24][C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[N:9]=[C:8]([CH3:10])[N:7]=2)=[O:12])=[CH:16][C:17]=1[O:22][CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 103713-PyridinecarboxaldehydeHCID 6451240Aluminum(III) ChlorideHCID 70978837HCID 70978837, compound

Product 1

HCID 70978720HCID 70978720, compoundYield 23.42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold solution of 6-acetyl-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide (0.050 g, 0.158 mmol, Preparation #23) and nicotinaldehyde (0.0168 mg, 0.158 mmol) in DCM (2 mL) was added aluminium chloride (0.02311 g, 0.173 mmol). The reaction mixture was allowed to stir for 15 minutes and added TEA (0.033 mL, 0.236 mmol). The reaction mixture was slowly warmed to RT and stirred for 3 h. The reaction mixture was heated to about 50° C. for 0.5 h then cooled to RT and poured into cold water (20 mL) and the product was extracted with diethyl ether (2×20 mL). The organic layer was washed successively with water (1×20 mL), brine (1×20 mL), dried over sodium sulphate and evaporated to dryness. The residue obtained was purified by preparative TLC eluting with 50% EtOAC/hexane to afford N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(3-(pyridin-3-yl)acryloyl)pyrimidine-4-carboxamide 0.015 g, (23.42%), 1H NMR (400 MHz, DMSO): δ 9.59 (bs, 1H) 9.00 (s, 1H) 8.67 (s, 1H) 8.33-8.17 (m, 3H) 8.00-7.96 (m, 1H) 7.52-7.51 (m, 1H) 7.19-7.17 (m, 2H) 6.92-6.91 (m, 1H) 4.51-4.49 (m, 2H) 3.82 (s, 3H) 2.89 (s, 3H), MS m/z: 407 (M+H)+.

Workup

  1. stirringstirred for 3 h
  2. temperatureThe reaction mixture was heated to about 50° C. for 0.5 h
  3. temperaturethen cooled to RT
  4. extractionthe product was extracted with diethyl ether (2×20 mL)
  5. washThe organic layer was washed successively with water (1×20 mL), brine (1×20 mL)
  6. dry with materialdried over sodium sulphate
  7. customevaporated to dryness
  8. customThe residue obtained
  9. customwas purified by preparative TLC
  10. washeluting with 50% EtOAC/hexane

Sources & evidence

ORD record
ord-3bac3349d4d74a0392e55a1615c9ad17
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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