Methanol → 8-(Cyclopropylamino)-6-[[4-(diethylamino)phenyl]amino]imidazo[1,2-b]pyridazine-3-carbonitrile
Reaction equation
[CH:1]1([N:4](CC2C=CC(OC)=CC=2)[C:5]2[C:6]3[N:7]([C:23]([C:26]#[N:27])=[CH:24][N:25]=3)[N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.CO>C(Cl)Cl>[CH:1]1([NH:4][C:5]2[C:6]3[N:7]([C:23]([C:26]#[N:27])=[CH:24][N:25]=3)[N:8]=[C:9]([NH:11][C:12]3[CH:13]=[CH:14][C:15]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[CH:16][CH:17]=3)[CH:10]=2)[CH2:3][CH2:2]1Participants
Procedure
A solution of 244A (5 mg, 10.38 μmol) in DCM (1 mL) was treated with TFA (1 mL, 12.9 mmol) and stirred at room temperature for three hours. The reaction mixture was concentrated and dissolved in a small amount of MeOH and purified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min., 20 min. gradient, monitored at 220 nm) to give Example 244, (1.2 mg, 22.12% yield). HPLC: Rt=3.178 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=362.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.09-11.33 (1H, m), 9.70 (1H, s), 8.15 (1H, s), 7.82-8.05 (2H, m), 7.51-7.67 (2H, m), 6.24 (1H, s), 1.01 (6H, t, J=6.80 Hz), 0.72-0.86 (2H, m, J=5.54 Hz), 0.53-0.72 (2H, m, J=2.77 Hz).
Workup
- concentrationThe reaction mixture was concentrated
- dissolutiondissolved in a small amount of MeOH
- custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min., 20 min. gradient, monitored at 220 nm)
- customto give Example 244, (1.2 mg, 22.12% yield)
Sources & evidence
- ORD record
- ord-44247042fc6a44b8b59998038d3f82d5
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08252795B2
Reaction notes
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