Ammonia → 2-(1-methyl-1H-pyrazol-4-yl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide
Reaction equation
Br[C:2]1[CH:3]=[C:4]([C:21]([NH2:23])=[O:22])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O.N>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O.COCCOC>[CH3:24][N:25]1[CH:29]=[C:28]([C:2]2[CH:3]=[C:4]([C:21]([NH2:23])=[O:22])[C:5]3[NH:6][C:7]4[CH:8]=[C:9]([N:15]5[CH2:20][CH2:19][O:18][CH2:17][CH2:16]5)[CH:10]=[CH:11][C:12]=4[C:13]=3[N:14]=2)[CH:27]=[N:26]1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
2-Bromo-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.12 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 mg, 0.24 mmol), and PdCl2(dppf)-CH2Cl2 adduct (9.79 mg, 0.012 mmol) in a microwave vial was flushed with nitrogen. DME (2 mL) and aq. Na2CO3 solution (0.30 mL, 0.60 mmol, 2.0 M) were added, the vial sealed, and heated at 100° C. for 3.5 hr. Preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, 10 to 70% gradient over 20 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH gave 2-(1-methyl-1H-pyrazol-4-yl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.075 mmol, 63% yield) as a solid. MS (ESI) m/z 377.20 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.12 (1H, s), 8.36 (1H, br. s.), 8.25 (1H, s), 8.05 (1H, s), 8.01 (1H, s), 7.99 (1H, d, J=8.85 Hz), 7.79 (1H, s), 7.19 (1H, d, J=2.14 Hz), 6.98 (1H, dd, J=8.85, 2.14 Hz), 3.93 (3H, s), 3.77-3.84 (4H, m), 3.20-3.25 (4H, m).
Sources & evidence
- ORD record
- ord-33af76226e5d4cb78109c9d63b685cca
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08815840B2
Reaction notes
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