Formaldehyde → 1-[4-Amino-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]ethanol

HRID 73669Notes

Reaction equation

[NH2:1][C:2]1[C:7]2=[CH:8][C:9]([CH:11]([OH:13])[CH3:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.[CH2:14]=O.O.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>CC(O)=O>[NH2:1][C:2]1[C:7]2=[CH:8][C:9]([CH:11]([OH:13])[CH3:12])=[C:10]([CH2:14][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of AcOH (70 mL) was added 1-(4-aminopyrrolo[2,1-f][1,2,4]triazin-6-yl)ethanol (611 mg, 3.43 mmol) followed by the addition of a 0.5 M solution of 37% formaldehyde in water (0.26 mL, 3.43 mmol) and morpholine (0.30 mL, 3.43 mmol) in AcOH (6.86 mL) was added. The reaction was heated to 60° C. for 1.5 h. The solution was allowed to cool to rt and was then evaporated via rotary evaporation chasing the remaining AcOH with toluene. The crude material was purified by column chromatography (85:15 v/v CH2Cl2-EtOAc) to afford 633 mg of the above compound (2.28 mmol, yield 67%). 1H-NMR (DMSO-d6) δ 7.79 (s, 1H), 7.57 (br s, 2H), 6.85 (s, 1H), 4.94 (m, 1H), 3.84 (m, 2H), 3.49 (m, 4H), 2.37 (m, 4H), 1.41 (d, J=6.6 Hz, 3H); MS [M+H]+=278.0; LCMS RT=1.01 min.

Workup

additionwas added
temperatureto cool to rt
customwas then evaporated via rotary evaporation
customThe crude material was purified by column chromatography (85:15 v/v CH2Cl2-EtOAc)

Sources & evidence

ORD record: ord-91601d4d2d3547fb80dce4de612f038f
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829185B2

Reaction notes

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