N,N-Dimethylaniline → 4-chloro-7H-pyrrolo(2,3-d)pyrimidin-2-amine
Reaction equation
[NH2:1][C:2]1[NH:3][C:4](=O)[C:5]2[CH:10]=[CH:9][NH:8][C:6]=2[N:7]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:23]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(#N)C>[Cl:23][C:4]1[C:5]2[CH:10]=[CH:9][NH:8][C:6]=2[N:7]=[C:2]([NH2:1])[N:3]=1Participants
Conditions
- Temperature
- 85 °C
Procedure
To a solution of 2-amino-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (5.00 g, 33.3 mmol), dimethylaniline (4.22 mL, 41.0 mmol) and benzyltriethylammonium chloride (15.2 g, 66.6 mmol) in acetonitrile (25 mL) at room temperature under argon was added POCl3 (18.6 mL, 200 mmol) dropwise for 30 min. The mixture was refluxed at 85° C. for 3 h and cooled to room temperature. The reaction was concentrated in vacuo to brown oil and to the oil was added an ice cold H2O (10 mL). The pH of the solution was adjusted to 5 by the addition of an aqueous NH4OH solution. Silica gel chromatography (CH2Cl2:MeOH=95:5) yielded 2.53 g (45%) of 4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine as a light yellow solid. The product was then benzylated at N7 using standard techniques.
Workup
- temperaturecooled to room temperature
- concentrationThe reaction was concentrated in vacuo to brown oil and to the oil
- additionwas added an ice cold H2O (10 mL)
- additionThe pH of the solution was adjusted to 5 by the addition of an aqueous NH4OH solution
Sources & evidence
- ORD record
- ord-c640c6e2807f4a2eb847cbca1f4ece68
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354532B2
Reaction notes
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