Phosphorus oxychloride → 6-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-chloro-N-isopropylpyrimidin-4-amine
Reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[CH:14]=[C:13]([NH:15][CH:16]([CH3:18])[CH3:17])[N:12]=[C:11](O)[N:10]=1)[CH2:2]2.O=P(Cl)(Cl)[Cl:22]>>[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:10]=[C:11]([Cl:22])[N:12]=[C:13]([NH:15][CH:16]([CH3:18])[CH3:17])[CH:14]=1)[CH2:2]2Participants
Conditions
- Temperature
- 100 °C
Procedure
In a 250 mL round-bottomed flask was placed 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(isopropylamino)pyrimidin-2-ol (29, 124 mg, 0.469 mmol) in POCl3 (20 ml) to give a yellow solution. The mixture was stirred at 100° C. for 16 h. The mixture was cooled to room temperature, concentrated, diluted with dichloromethane and washed with saturated NaHCO3 followed by 0.2 N NaOH. The organic phase was dried over MgSO4, filtered and concentrated to give the title compound (91 mg, 69%). Aryl chloride 30 could be transformed into aniline 18 as described in scheme 2 for the conversion of 5 into 6. Aniline 18 could be transformed into urea or carbamate compounds as described in scheme 2 (and illustrated in the experimental section for scheme 7).
Workup
- customIn a 250 mL round-bottomed flask was placed
- temperatureThe mixture was cooled to room temperature
- concentrationconcentrated
- additiondiluted with dichloromethane
- washwashed with saturated NaHCO3
- dry with materialThe organic phase was dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-01b4b233b3554daa897591397ae627ff
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835429B2
Reaction notes
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