Formaldehyde → [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](4-methylpiperazin-1-ylmethyl)amine

HRID 705562Notes

Reaction equation

HRID 705562 reaction equation
[CH2:1]=O.[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[F:10][C:11]1[C:12]([NH2:26])=[N:13][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[N:15][CH:16]=1>C(Cl)Cl>[F:10][C:11]1[C:12]([NH:26][CH2:3][N:4]2[CH2:9][CH2:8][N:7]([CH3:1])[CH2:6][CH2:5]2)=[N:13][C:14]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 531671-MethylpiperazineHCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818795[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](4-methylpiperazin-1-ylmethyl)amineYield 30.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a magnetically stirred mixture of paraformaldehyde (0.24 g, 8 mmol) in CH2Cl2 (20 mL) was added N-methylpiperazine (0.80 g, 8.0 mmol). The suspension was stirred overnight at ambient temperature on an orbital shaker, and then 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.47 g, 2.0 mmol) was added. The resulting mixture was stirred over the weekend at RT. The solvent was evaporated and the crude residue was washed twice with 50% ether/petroleum ether and dried under a stream of N2 to give 0.21 g (30%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](4-methylpiperazin-1-ylmethyl)amine as a beige solid: mp 125-126° C.; 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=2.3 Hz, 1H), 7.43 (m, 2H), 7.03 (t, J=8.5 Hz, 2H), 5.40 (bs, 1H), 5.27 (s, 2H), 4.41 (d, J=6.8 Hz, 2H), 2.63 (bs, 4H), 2.47 (bs, 4H), 2.30 (s, 3H); HPLC-MS (ESI) m/z 350 (M+H)+.

Workup

  1. stirringThe resulting mixture was stirred over the weekend at RT
  2. customThe solvent was evaporated
  3. washthe crude residue was washed twice with 50% ether/petroleum ether
  4. dry with materialdried under a stream of N2

Sources & evidence

ORD record
ord-14d2cc09b021431fb259e622cee35d8e
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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