Triethylamine → N'-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N-dimethyl-propionamidine

HRID 1500021Notes

Reaction equation

HRID 1500021 reaction equation
[CH3:1][N:2]([CH3:7])[C:3](=O)[CH2:4][CH3:5].P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[F:20][C:21]1[C:22]([NH2:36])=[N:23][C:24]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)=[N:25][CH:26]=1>C(Cl)(Cl)Cl>[F:20][C:21]1[C:22]([N:36]=[C:3]([N:2]([CH3:7])[CH3:1])[CH2:4][CH3:5])=[N:23][C:24]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)=[N:25][CH:26]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12965Propanamide, N,N-dimethyl-HCID 24813Phosphorus oxychlorideHCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818713N'-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N-dimethyl-propionamidineYield 32.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of N,N-dimethylpropionamide (0.202 g, 2.0 mmol) in CHCl3 (2 mL) was added phosphorous oxychloride (POCl3, 0.066 g, 0.43 mmol) and the mixture was agitated on an orbital shaker at room temperature for 1 h. Triethylamine (0.22 g, 2.2 mmol) and 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.40 mmol) were added, and the mixture was agitated at 50° C. for 3 h, cooled to room temperature, partitioned between chloroform and water, the phases separated, and the organics evaporated under reduced pressure. Purification by reverse phase chromatography afforded the title compound (0.042 g, 31% yield) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.46-7.40 (m, 2H), 7.07-6.99 (m, 2H), 5.30 (s, 2H), 3.13 (s, 6H), 2.55 (q, J=7.7 Hz, 2H), 1.15 (t, J=7.7 Hz, 3H); HPLC-MS (ESI) m/z 321 (M+H)+.

Workup

  1. stirringthe mixture was agitated at 50° C. for 3 h
  2. temperaturecooled to room temperature
  3. custompartitioned between chloroform and water
  4. customthe phases separated
  5. customthe organics evaporated under reduced pressure
  6. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-1dff3750e2014d13a69b4404b241d2ef
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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