Nitrogen → HCID 11805816, compound

HRID 1761051Notes

Reaction equation

HRID 1761051 reaction equation
C(OC([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)(C)(C)C.[C:19]([O:23]CC1C=CC=CC=1)(=[O:22])[CH:20]=[CH2:21].CCN(C(C)C)C(C)C.N#N>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[N:16]1[C:17]2[NH:8][CH2:9][CH2:10][CH2:11][C:12]=2[CH:13]=[C:14](/[CH:21]=[CH:20]/[C:19]([OH:23])=[O:22])[CH:15]=1

Participants

8

Reactant 4

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

Product 1

HCID 11805816HCID 11805816, compoundYield 103.9%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 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, 16.5 Hz, 2H), 1.93 (m, 2H), 1.54 (s, 9H)

Workup

  1. temperaturethen heated to reflux
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-319e2f8bcd6c4f4599f89c4e12e8464a
Source dataset
uspto-grants-2005_01
Patent number
US06846819B1

Reaction notes

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