Ammonia → HCID 66604493, compound

HRID 2410829Notes

Reaction equation

HRID 2410829 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:18]([NH2:20])=[O:19])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([N:15]([CH3:17])[CH3:16])[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29].C([O-])([O-])=O.[Na+].[Na+].N>CN(C=O)C.O.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.C(#N)C.COCCOC>[Cl:21][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[C:4]([C:18]([NH2:20])=[O:19])[C:5]3[NH:6][C:7]4[CH:8]=[C:9]([N:15]([CH3:17])[CH3:16])[CH:10]=[CH:11][C:12]=4[C:13]=3[N:14]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]

Participants

11

Reactant 4

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 86663055HCID 86663055, compound

Product 1

HCID 66604493HCID 66604493, compoundYield 80%

Reagents, catalysts & solvents 6

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial containing a mixture of 2-bromo-7-(dimethylamino)-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.090 mmol), 3-chloro-4-methoxyphenylboronic acid (34 mg, 0.18 mmol), PdCl2(dppf)-CH2Cl2 adduct (7.4 mg, 9.0 μmol) was flushed with nitrogen. DME (1.5 mL) and Na2CO3 (0.23 mL, 0.45 mmol, 2.0 M aq. solution) were added and the vial was sealed and heated at 100° C. in an oil bath for 2 hrs. This was diluted with DMF and preparative HPLC (PHENOMENEX® Luna C18 30×100 10u Column, Solvent A=10 mM NH4OAc in 95% water:5% acetonitrile; B=10 mM NH4OAc in 5% water:95% acetonitrile, 30 to 100% B over 20 min at 30 mL/min) followed by SCX capture and release with 2 N solution NH3 in MeOH afforded 2-(3-chloro-4-methoxyphenyl)-7-(dimethylamino)-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.072 mmol, 80% yield) as a yellow solid. MS (ESI) m/z 395.12 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.10 (1H, s), 8.49 (1H, s), 8.33 (1H, d, J=2.14 Hz), 8.16-8.27 (2H, m), 8.02 (1H, d, J=8.55 Hz), 7.78 (1H, s), 7.31 (1H, d, J=8.55 Hz), 6.99 (1H, d, J=2.14 Hz), 6.79 (1H, dd, J=8.85, 2.14 Hz), 3.95 (3H, s), 3.04 (6H, s).

Workup

  1. additionA microwave vial containing
  2. customwas flushed with nitrogen
  3. customthe vial was sealed

Sources & evidence

ORD record
ord-921011f121f748de992f4e7e04892369
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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