Dimethylacetamide → 6-chloro-8-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:3]=1[NH2:16].CN(C)[C:19](=O)[CH3:20].C(C(CC)(CC)C([O-])([O-])[O-])C>C(O)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]2[C:3]=1[N:16]=[C:19]([CH3:20])[N:9]2[CH:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1Participants
Conditions
- Temperature
- 160 °C
Procedure
In an alternative procedure, the reaction was carried out in parallel using 10 vials. To each vial was added 6-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine (preparation Route A) (400 mg, 1.64 mmol), N,N-dimethyl acetamide (8 mL), glacial acetic acid (16 μL, 0.2% vol) and triethylorthoacetate (0.8 mL, 5.32 mmol) and the mixture was stirred at 160° C. After 3 days, the reaction was complete (by LC-MS) and the reaction mixture, containing desired product MS (EI) m/z 268.1 (MH)+, as well as acetylated product MS (EI) m/z 310.2 (MH)+, was cooled to room temperature. To each vial was then added 1 mL of a 1 M aqueous solution of HCl, with stirring at 100° C. After 1 h at 100° C., LC-MS analysis indicated only desired product, in a clean reaction. Upon cooling to room temperature, a white precipitate formed. Filtration under vacuum, followed by washing of the precipitate with portions of methanol provided the desired product (combined yield 2.98 g for 10 vials, 68% yield) as a white solid in pure form. 1HNMR (300 MHz, d6-DMSO) δ, ppm: 6.76 (s, 2H), 4.41 (m, 1H), 3.97 (m, 2H), 3.45 (m, 2H), 3.33 (s, 3H), 2.63 (m, 2H), 1.74 (m, 2H); MS (EI) m/z 268.1 (MH)+.
Sources & evidence
- ORD record
- ord-644af6f5c39a4449bdb82826cf5738b6
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07902187B2
Reaction notes
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