5-bromo-1H-pyrrolo[2,3-b]pyridine → HCID 22714597, compound

HRID 514302Notes

Reaction equation

HRID 514302 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][O:8][C:5]2=[N:6][CH:7]=1.Br[C:12]1[CH:13]=[C:14]2[CH:20]=[CH:19][NH:18][C:15]2=[N:16][CH:17]=1.[CH3:21][N:22]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:23]([CH2:25][CH:26]=[CH2:27])[CH3:24]>[Pd]>[CH3:21][N:22]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH:23]([CH2:25]/[CH:26]=[CH:27]/[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][O:8][C:5]2=[N:6][CH:7]=1)[CH3:24].[CH3:21][N:22]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH:23]([CH2:25]/[CH:26]=[CH:27]/[C:12]1[CH:13]=[C:14]2[CH:20]=[CH:19][NH:18][C:15]2=[N:16][CH:17]=1)[CH3:24]

Participants

6

Reactant 3

HCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 106794495-Bromofuro[2,3-b]pyridineHCID 15546849N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine

Product 2

HCID 22714597HCID 22714597, compoundHCID 22714600HCID 22714600, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Other polycyclic aromatic compounds of the present invention can be prepared by the Heck reaction. Thus both 5-bromofuro[2,3-b]pyridine and 5-bromo-1H-pyrrolo[2,3-b]pyridine can undergo palladium catalyzed coupling with the previously described olefinic amine side chain, N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine, to give (4E)-N-methyl-N-(tert-butoxycarbonyl)-5-(5-furo[2,3-b]pyridinyl)-4-penten-2-amine and (4E)-N-methyl-N-(tert-butoxycarbonyl)-5-(5-1H-pyrrolo[2,3-b]pyridinyl)-4-penten-2-amine respectively. Subsequent removal of the tert-butoxycarbonyl group with trifluoroacetic acid will provide (4E)-N-methyl-5-(5-furo[2,3-b]pyridinyl)-4-penten-2-amine and (4E)-N-methyl-5-(5-1H-pyrrolo[2,3-b]pyridinyl)-4-penten-2-amine. The requisite 5-bromofuro[2,3-b]pyridine and 5-bromo-1H-pyrrolo[2,3-b]pyridine can be made from 2,3-dihydrofuro[2,3-b]pyridine and 2,3-dihydropyrrolo[2,3-b]pyridine respectively, by bromination (bromine and sodium bicarbonate in methanol) and dehydrogenation (2,3-dichloro-5,6-dicyano-1,4-benzoquinone), using chemistry described by E. C. Taylor et al., Tetrahedron 43: 5145-5158 (1987). 2,3-Dihydrofuro[2,3-b]pyridine and 2,3-dihydropyrrolo[2,3-b]pyridine are, in turn, made from 2-chloropyrimidine (Aldrich Chemical Company), as described by A. E. Frissen et al., Tetrahedron 45: 803-812 (1989), by nucleophilic displacement of the chloride (with the sodium salt of 3-butyn-1-ol or with 4-amino-1-butyne) and subsequent intramolecular Diels-Alder reaction. Using similar chemistry, 2,3-dihydrofuro[2,3-b]pyridine and 2,3-dihydropyrrolo[2,3-b]pyridine are also produced from 3-methylthio-1,2,4-triazene (E. C. Taylor et al., Tetrahedron 43: 5145-5158 (1987)), which in turn is made from glyoxal and S-methylthiosemicarbazide (W. Paudler et al., J. Heterocyclic Chem. 7: 767-771 (1970)).

Sources & evidence

ORD record
ord-4828c011bbfa49738983d190f1a13856
Source dataset
uspto-grants-2015_08
Patent number
US09107915B2

Reaction notes

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