2-Amino-4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine synthesis

Yield:204929-06-6 88 %

Reaction Conditions:

with trichlorophosphate in N,N-dimethyl-aniline;Reflux;

Steps:

Intermediate 3: 4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Intermediate 3: 4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine
To a 1 L round bottom flask were added Intermediate 2 (25.0 g, 152.3 mmol), phosphorus oxychloride (250 ml) and N,N-dimethylaniline (0.69 ml, 5.5 mmol).
The mixture was heated to reflux for 3 h after which time the reaction mixture was cooled and excess phosphorus oxychloride was removed under reduced pressure.
The remaining material was carefully poured onto 500 ml crushed ice then basified with 25% aqueous ammonia (～400 ml).
The resulting precipitate was collected by filtration and dried under high vacuum with phosphorus pentoxide to constant weight to give 4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Intermediate 3) (24.55 g, 88%) as a light brown solid.
LCMS: Rt 2.45 min, m/z: [M+H]+ Calcd for C₇H₇ClN₄ 183.04; Found 183.10.
¹H-NMR (400 MHz, DMSO-d6): 2.27 (d, 3H, CH₃, J 0.8Hz), 5.93 (q, 1H, ArH, J 0.8Hz), 6.35 (bs, 2H, NH₂), 11.42 (bs (1H, NH).

References:

EP4092030,2022,A1 Location in patent:Paragraph 0065-0067