Ammonia → HCID 66604492, compound

HRID 2410847Notes

Reaction equation

HRID 2410847 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[C:14]([C:31]([NH2:33])=[O:32])[C:15]3[NH:16][C:17]4[CH:18]=[C:19]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)[CH:20]=[CH:21][C:22]=4[C:23]=3[N:24]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10]Cl.[I-].[K+].C([O-])([O-])=O.[K+].[K+].[CH2:42]1[CH2:48][O:47][CH2:46][CH2:45][NH:44][CH2:43]1.Cl.C(O)(C(F)(F)F)=O.N>CS(C)=O.CO.O>[O:47]1[CH2:48][CH2:42][CH2:43][N:44]([CH2:10][CH2:9][O:8][C:7]2[CH:6]=[CH:5][C:4]([C:12]3[CH:13]=[C:14]([C:31]([NH2:33])=[O:32])[C:15]4[NH:16][C:17]5[CH:18]=[C:19]([N:25]6[CH2:30][CH2:29][O:28][CH2:27][CH2:26]6)[CH:20]=[CH:21][C:22]=5[C:23]=4[N:24]=3)=[CH:3][C:2]=2[Cl:1])[CH2:45][CH2:46]1

Participants

10

Reactant 6

HCID 222AmmoniaHCID 4875Potassium IodideHCID 6422Trifluoroacetic acid2×HCID 11430Potassium CarbonateHCID 230902141,4-Oxazepane hydrochlorideHCID 66605767HCID 66605767, compound

Product 1

HCID 66604492HCID 66604492, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent3×HCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(3-chloro-4-(2-chloroethoxy)phenyl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (20 mg, 0.041 mmol), potassium iodide (14 mg, 0.082 mmol), K2CO3 (11 mg, 0.082 mmol) and homomorpholine hydrochloride (23 mg, 0.17 mmol) in DMSO (0.2 mL) in a vial was heated at 70° C. for 40 hrs. 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, gradient of 0 to 60% B over 20 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 2-(4-(2-(1,4-oxazepan-4-yl)ethoxy)-3-chlorophenyl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (16 mg, 0.029 mmol, 71% yield) as a yellow solid. MS (ESI) m/z 550.24 (M+H). 1H NMR (500 MHz, MeOD) δ ppm 8.22 (1H, d, J=8.85 Hz), 8.16 (1H, d, J=2.14 Hz), 8.06 (1H, s), 7.99 (1H, dd, J=8.55, 2.44 Hz), 7.19 (1H, d, J=8.85 Hz), 7.10 (1H, d, J=2.14 Hz), 7.03 (1H, dd, J=8.85, 2.14 Hz), 4.27 (2H, t, J=5.34 Hz), 3.86-3.94 (4H, m), 3.76-3.85 (4H, m), 3.27-3.31 (4H, m), 3.10 (2H, t, J=5.34 Hz), 2.94-3.02 (4H, m), 1.97 (2H, m).

Sources & evidence

ORD record
ord-2414c608a5cc4dd19ab65afc05076ab5
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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