Sodium Carbonate → 7-Bromo-4-[1-(2,5-difluorophenyl)methylidene]-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 659466Notes

Reaction equation

HRID 659466 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[Br:7][C:8]1[N:17]=[C:16]2[C:11]([C:12](=[CH:18]I)[CH2:13][CH2:14][NH:15]2)=[CH:10][CH:9]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1B(O)O.C(OCC)(=O)C.CCCCCC>C1(C)C=CC=CC=1.C(O)C.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>[Br:7][C:8]1[N:17]=[C:16]2[C:11]([C:12](=[CH:18][C:25]3[CH:26]=[C:21]([F:20])[CH:22]=[CH:23][C:24]=3[F:27])[CH2:13][CH2:14][NH:15]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 21226206Ethyl acetate hexaneHCID 767246547-Bromo-4-[1-iodomethylidene]-1,2,3,4-tetrahydro-[1,8]naphthyridine

Product 1

HCID 767246537-Bromo-4-[1-(2,5-difluorophenyl)methylidene]-1,2,3,4-tetrahydro-[1,8]naphthyridineYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Procedure

Na2CO3 (2N, 3.46 mL, 10.0 eq) was added to a mixture of 7-bromo-4-[1-iodomethylidene]-1,2,3,4-tetrahydro-[1,8]naphthyridine (607 mg), 2,5-difluorophenylboronic acid (328 mg, 1.2 eq), and Pd(PPh3)4 (150 mg, 0.075 eq) in toluene/ethanol (4:1 v/v). The reaction was heated at 85° C. for five (5) hours, Celite was added, and the mixture was then concentrated under reduced pressure. The dry powder was then dry loaded onto a silica gel column and a gradient of 0-20% ethyl acetate/hexane as the eluting solvent gave the title compound as a yellow solid (70% yield). M.p. 178-179° C., LCMS: m/z=337 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.62 (t, J=5.8 Hz, 2H), 3.55-3.62 (m, 2H), 5.25 (bs, 1H), 6.26 (s, 1H), 6.45 (d, J=7.9 Hz, 1H), 6.85-6.95 (m, 1H), 6.96-7.12 (m, 3H).

Workup

  1. additionwas added
  2. concentrationthe mixture was then concentrated under reduced pressure
  3. customThe dry powder was then dry

Sources & evidence

ORD record
ord-ec4c9cf107204ef898e681d6d7a967eb
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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