Nitrogen → HCID 10938089, compound

HRID 1920973Notes

Reaction equation

HRID 1920973 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14](Br)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:19]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:22])[CH:20]=[CH2:21].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C.N#N>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6]([N:8]1[C:17]2[N:16]=[CH:15][C:14](/[CH:21]=[CH:20]/[C:19]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])=[CH:13][C:12]=2[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 947NitrogenHCID 75617Benzyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 11833959tert-Butyl 6-bromo-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Product 1

HCID 10938089HCID 10938089, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-6-bromo-1,2,3,4-tetrahydro-1,8-naphthyridine (1.79 g, 5.70 mmole), benzyl acrylate (1.11 g, 6.84 mmole), Pd(OAc)2 (65 mg, 0.29 mmole), P(o-tolyl)3 (173 mg, 0.57 mmole), and (i-Pr)2NEt (2.5 mL, 14.25 mmole) in propionitrile (30 mL) was degassed (3×N2/vacuum) then heated to reflux. After 18 hr the mixture was cooled to RT and concentrated. Flash chromatography on silica gel (25% EtOAc/hexanes) gave the title compound (1.21 g, 54%) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.65 (d, J=16.0 Hz, 1H), 7.53 (s, 1H), 7.40 (m, 5H), 6.43 (d, J=16.0 Hz, 1H), 5.25 (s, 2H), 3.77 (m, 2H), 2.75 (t, J=63 Hz, 2H), 1.93 (m, 2H), 1.54 (s, 9H)

Workup

  1. temperaturethen heated to reflux
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-6697b8082f4f4b3c8d41a10a4ba45de2
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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