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

HRID 705576Notes

Reaction equation

HRID 705576 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-58d3547873434a3182d4bd97e89fa991
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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