3-Bromopyridine → HCID 24901063, compound

HRID 1158738Notes

Reaction equation

HRID 1158738 reaction equation
[NH2:1][C:2]1[C:3]([C:15]([NH2:17])=[O:16])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[N:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N[C@@H:27]1[CH2:32][CH2:31][CH2:30]C[C@H:28]1[NH2:33].BrC1C=NC=CC=1>[Cu]I.O1CCOCC1>[NH2:1][C:2]1[C:3]([C:15]([NH2:17])=[O:16])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([C:27]3[CH:28]=[N:33][CH:30]=[CH:31][CH:32]=3)[C:6]=2[N:14]=1

Participants

7

Reactant 4

HCID 122863-BromopyridineHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 152709842-amino-9H-pyrido[2,3-b]indole-3-carboxamide

Product 1

HCID 24901063HCID 24901063, compoundYield 164.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred mixture of 2-amino-9H-pyrido[2,3-b]indole-3-carboxamide (5, 100 mg, 0.44 mmol), Copper(I) iodide (8 mg, 0.045 mmol) and potassium phosphate (190 mg, 0.88 mmol) under dry nitrogen was added (±)-trans-1,2-diaminocyclohexane (5 μL, 0.04 mmol) and 3-bromopyridine (43 μL, 0.442 mmol), followed by 1,4-dioxane (2 mL). The mixture was heated at 110° C. for 2 days. The reaction mixture was cooled to room temperature, extracted with methylene chloride (3×30 ml) and washed with water. The extracts were combined, dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography (12 g silica, methylene chloride to 90/10 methylene chloride/methanol gradient) to yield 2-amino-9-pyridin-3-yl-9H-pyrido[2,3-b]indole-3-carboxamide (67, 20 mg, 10%). NH4OAc standard conditions. DAD Retention time =5.99 min. M+H=310. 1H NMR (300 MHz, MeOD): δ 8.86 (d, J=2.4 Hz, 1H), 8.74 (s, 1H), 8.66-8.63 (m, 1H), 8.14 (d, J=8.2 Hz, 1H), 7.96 (d, J=7.0 Hz, 1H), 7.70 (dd, J=4.7, 8.2 Hz, 1H), 7.36-7.28 (m, 4H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with methylene chloride (3×30 ml)
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (12 g silica, methylene chloride to 90/10 methylene chloride/methanol gradient)

Sources & evidence

ORD record
ord-43a971bcdf824028a538d40d2ddcbdbe
Source dataset
uspto-grants-2010_10
Patent number
US07812018B2

Reaction notes

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