Formaldehyde → 6-Methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 73704Notes

Reaction equation

HRID 73704 reaction equation
[CH2:1]=O.[CH2:3]1[CH2:9][O:8][CH2:7][CH2:6][NH:5][CH2:4]1.Cl.[CH3:11][C:12]1[CH:13]=[C:14]2[N:19]([CH:20]=1)[N:18]=[CH:17][N:16]=[C:15]2[NH2:21]>CC(O)=O>[CH3:11][C:12]1[CH:13]=[C:14]2[N:19]([C:20]=1[CH2:1][N:5]1[CH2:4][CH2:3][CH2:9][O:8][CH2:7][CH2:6]1)[N:18]=[CH:17][N:16]=[C:15]2[NH2:21]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 230902141,4-Oxazepane hydrochlorideHCID 552886216-Methylpyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 579552106-Methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 78%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

A solution of formaldehyde (0.61 mL, 8.10 mmol, 37% in H2O) and homomorpholine hydrochloride (1.11 g, 8.10 mmol) in AcOH (5 mL) was added to a stirring solution of 6-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine (1.00 g, 6.75 mmol) in AcOH (5 mL) at 60° C. The reaction was allowed to stir until all starting material had been consumed as shown by HPLC (1 hr). The reaction mixture was worked up by diluting with EtOAc and washing 3× with saturated sodium carbonate solution. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was triturated with Et2O to obtain 1.37 g (78%) of a light brown powder. 1H-NMR (DMSO-d6) δ 7.76 (s, 1H), 7.47 (br s, 2H), 6.65 (s, 1H), 3.85 (s, 2H), 3.62 (t, J=5.7 Hz, 2H), 3.55-3.51 (m, 2H), 2.61-2.55 (m, 4H), 2.21 (s, 3H), 1.77-1.74 (m, 2H); MS [M+H]+=262.0; LCMS RT=1.02.

Workup

  1. customhad been consumed
  2. customas shown by HPLC (1 hr)
  3. additionby diluting with EtOAc
  4. washwashing 3× with saturated sodium carbonate solution
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was triturated with Et2O

Sources & evidence

ORD record
ord-72629167bff4445686cb3d7e42dc5442
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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