Triethylamine → 2-phenyl-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,8-naphthyridine

HRID 875046Notes

Reaction equation

HRID 875046 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4](C(OC(C)(C)C)=O)[CH:3]=1.C(N(CC)CC)C.CC1(C)C(C)(C)OBO1.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:41]1[CH:50]=[CH:49][N:48]=[C:47]2[C:42]=1[CH:43]=[CH:44][C:45]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[N:46]2>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC.O.O1CCOCC1>[C:51]1([C:45]2[CH:44]=[CH:43][C:42]3[C:47](=[N:48][CH:49]=[CH:50][C:41]=3[C:2]3[C:10]4[C:5](=[N:6][CH:7]=[CH:8][CH:9]=4)[NH:4][CH:3]=3)[N:46]=2)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 23529164tert-Butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylateHCID 684608095-Chloro-2-phenyl-1,8-naphthyridine

Product 1

HCID 590536492-phenyl-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,8-naphthyridine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A Schlenk tube is filled successively under nitrogen with 189 mg (0.55 mmol) of tert-butyl 3-iodopyrrolo[2,3-b]pyridine-1-carboxylate, 9.5 mg (8.2 μmol) of tetrakis(triphenylphosphine)palladium, 2.3 ml of dioxane, 0.23 ml (1.6 mmol) of triethylamine and 80 μml (0.55 mmol) of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane. The reaction mixture is stirred at 80° C. for 3 hours under nitrogen. The reaction mixture is cooled to room temperature; 1 ml of water, 175 mg (2.1 mmol) of sodium carbonate, 22 mg (19 μmol) of tetrakis(triphenylphosphine)palladium, 132 mg (0.55 mmol) of 5-chloro-2-phenyl-1,8-naphthyridine and 4.6 ml of 1,2-dimethoxyethane are added under a nitrogen atmosphere. The reaction mixture is stirred at 100° C. for 20 hours. The reaction mixture is cooled to room temperature and evaporated in vacuo. The residue is chromatographed on a silica-gel column with methanol/dichloromethane as eluent: 2-phenyl-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,8-naphthyridine (“A5”) as yellowish crystals; MS (ESI): 322 [M+H]+;

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. stirringThe reaction mixture is stirred at 100° C. for 20 hours
  3. temperatureThe reaction mixture is cooled to room temperature
  4. customevaporated in vacuo
  5. customThe residue is chromatographed on a silica-gel column with methanol/dichloromethane as eluent

Sources & evidence

ORD record
ord-036959ecb5ec4323a0deee2ebb6019c0
Source dataset
uspto-grants-2015_03
Patent number
US08981101B2

Reaction notes

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