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

Temperature

60 °C

Pyrrolo[2,1-f][1,2,4]triazin-4-amine (4000 mg, 29.8 mmol) was dissolved in acetic acid (160 mL). 37% wt formaldehyde in water is added (2.90 mL, 35.8 mmol) followed by 1,4-oxazepane hydrochloride (4.92 g, 35.8 mmol) and potassium acetate (5.27 g, 53.7 mmol). The reaction was heated at 60° C. under a nitrogen atmosphere overnight then cooled to room temperature. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc (300 mL) and saturated aqueous bicarbonate (150 mL). The aqueous layer is extracted with EtOAc (5×100 mL). The combined organics were washed with brine (100 mL) then dried with Na2SO4 to yield 6.78 g (92%) of desired product.

1. additionis added (2.90 mL, 35.8 mmol)
2. temperaturethen cooled to room temperature
3. concentrationThe reaction was concentrated under vacuum
4. customThe residue was partitioned between EtOAc (300 mL) and saturated aqueous bicarbonate (150 mL)
5. extractionThe aqueous layer is extracted with EtOAc (5×100 mL)
6. washThe combined organics were washed with brine (100 mL)
7. dry with materialthen dried with Na2SO4

ORD record

ord-86692ddaaf5b4864aba9cf106d7e340d

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143393B2