Acetic Acid → HCID 86694434, compound
Reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10]CC2C=CC=CC=2)=O)[CH:4]2[CH2:18][CH2:19][N:20]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH:3]12.Br.C(O)(=O)C.C1CCN2[C:38](=[N:39]CCC2)[CH2:37]C1.C(CC(OC)=O)#N>>[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:10])[CH2:37][C:38]#[N:39])[CH:4]2[CH2:18][CH2:19][N:20]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH:3]12Participants
Procedure
To the product of Example 20 (30 mg, 0.077 mmol), was added HBr in acetic acid (1.5 mL, 0.10 mmol) and the reaction was stirred at room temperature for 2 hours before being concentrated in vacuo and azeotroped with heptanes (×4) and MeOH/heptanes (×3). The solid was dried under high vacuum and was then dissolved in methanol and passed through a Varian StratoSpheres™ SPE PL-HCO3 MP SPE resin and concentrated in vacuo. The solid was dissolved in MeOH (0.4 mL) and DBU (5.8 μL, 0.038 mmol) and methyl cyanoacetate (15.2 mg, 0.153 mmol) were added and the reaction was stirred at 40° C. for 16 hours. The reaction was concentrated in vacuo and the residue was purified by mass triggered reverse phase HPLC. Lyophilization of the desired fractions gave the title product (TFA salt) as a off-white solid. LRMS calc'd for C17H21N6O [M+H]+, 325; found 325. Jak1 activity: +.
Workup
- concentrationbefore being concentrated in vacuo
- customazeotroped with heptanes (×4) and MeOH/heptanes (×3)
- customThe solid was dried under high vacuum
- dissolutionwas then dissolved in methanol
- concentrationconcentrated in vacuo
- dissolutionThe solid was dissolved in MeOH (0.4 mL)
- stirringthe reaction was stirred at 40° C. for 16 hours
- concentrationThe reaction was concentrated in vacuo
- customthe residue was purified by mass triggered reverse phase HPLC
Sources & evidence
- ORD record
- ord-f41689e9612a4fcdb389bfeb688063a4
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08937077B2
Reaction notes
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