Toluene → 8-(6-(((2,6-diisopropylphenyl)amino)methyl)pyridin-2-yl)-N-phenyl-1,2,3,4-tetrahydronaphthalen-1-amine

HRID 928638Notes

Reaction equation

C([O-])([O-])=O.[Na+].[Na+].C[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][C:23]=2B2OC(C)(C)C(C)(C)O2)[CH2:18][CH2:17][CH2:16]1.Br[C:35]1[N:40]=[C:39]([CH2:41][NH:42][C:43]2[C:48]([CH:49]([CH3:51])[CH3:50])=[CH:47][CH:46]=[CH:45][C:44]=2[CH:52]([CH3:54])[CH3:53])[CH:38]=[CH:37][CH:36]=1.C1(C)C=CC=CC=1>O.CO.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>[CH:52]([C:44]1[CH:45]=[CH:46][CH:47]=[C:48]([CH:49]([CH3:51])[CH3:50])[C:43]=1[NH:42][CH2:41][C:39]1[N:40]=[C:35]([C:23]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:24]=2[CH:15]([NH:14][C:9]2[CH:8]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:16][CH2:17][CH2:18]3)[CH:36]=[CH:37][CH:38]=1)([CH3:54])[CH3:53]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 3.60 g (34.0 mmol) of Na2CO3 in a mixture of 150 ml of water and 45 ml of methanol was purged with argon for 30 min. The obtained solution was added to a mixture of 5.00 g (14.0 mmol) of N-(2-methylphenyl)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydronaphthalen-1-amine, 4.85 g (14.0 mmol) of N-[(6-bromopyridin-2-yl)methyl]-2,6-diisopropylaniline, 0.80 g (0.70 mmol) of Pd(PPh3)4, and 180 ml of toluene in argon atmosphere. This mixture was stirred for 12 h at 70° C. and then cooled to room temperature. The organic layer was separated, the aqueous layer was extracted with 3×50 ml of ethyl acetate. The combined organic extract was washed with brine, dried over Na2SO4, and evaporated to dryness. The residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate-triethylamine=100:10:1, vol.). Yield 2.50 g (36%) of a yellow oil. Anal. Calc. for C35H41N3: C, 83.45; H, 8.20; N, 8.34. Found: C, 83.69; H, 8.08; N, 8.13.1H NMR (CDCl3): δ 7.62-7.63 (m, 1H, 7-H in tetrahydronaphtalene); 7.55-7.58 (m, 1H, 4-H in Py); 7.52-7.54 (m, 1H, 3-H in Py); 7.41-7.44 (m, 1H, 6-H in tetrahydronaphtalene); 7.37-7.39 (m, 1H, 5-H in Py); 7.15-7.16 (m, 1H, 5-H in tetrahydronaphtalene); 7.03-7.10 (m, 4H, 3,4,5-H in 2,6-diisopropylphenyl and 5-H in 2-methylphenyl); 6.93 (m, 1H, 3-H in 2-methylphenyl); 6.70 (m, 1H, 6-H in 2-methylphenyl); 6.59 (m, 1H, 4-H in 2-methylphenyl); 5.35 (m, 1H, 1-H in tetrahydronaphtalene); 3.94-4.03 (m, 2H, CH2); 3.92-3.94 (m, 1H, 4- or 4′-H in tetrahydronaphtalene); 3.68-3.70 (m, 1H, 4′- or 4-H in tetrahydronaphtalene); 3.30 (sept, J=6.8 Hz, 2H, CH in 2,6-diisopropylphenyl); 3.16-3.24 (m, 1H, 3- or 3′-H in tetrahydronaphtalene); 2.92-3.00 (m, 1H, 3′- or 3-H in tetrahydronaphtalene); 2.38-2.47 (m, 1H, 2- or 2′-H in tetrahydronaphtalene); 2.14-2.22 (m, 1H, 2′- or 2-H in tetrahydronaphtalene); 1.75 (s, 3H, CH3 in 2-methylphenyl); 1.18-1.22 (m, 12H, CH3 in 2,6-diisopropylphenyl).

Workup

customwas purged with argon for 30 min
temperaturecooled to room temperature
customThe organic layer was separated
extractionthe aqueous layer was extracted with 3×50 ml of ethyl acetate
extractionThe combined organic extract
washwas washed with brine
dry with materialdried over Na2SO4
customevaporated to dryness
customThe residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate-triethylamine=100:10:1, vol.)

Sources & evidence

ORD record: ord-2c4af402ff684843bf8a954149784cdf
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290519B2

Reaction notes

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