Toluene → 7-(6-(((2,6-diisopropylphenyl)amino)methyl)pyridin-2-yl)-N-phenyl-2,3-dihydro-1H-inden-1-amine

HRID 630433Notes

Reaction equation

HRID 630433 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[C:7]1([NH:13][CH:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3B3OC(C)(C)C(C)(C)O3)[CH2:16][CH2:15]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:33]1[N:38]=[C:37]([CH2:39][NH:40][C:41]2[C:46]([CH:47]([CH3:49])[CH3:48])=[CH:45][CH:44]=[CH:43][C:42]=2[CH:50]([CH3:52])[CH3:51])[CH:36]=[CH:35][CH:34]=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:47]([C:46]1[CH:45]=[CH:44][CH:43]=[C:42]([CH:50]([CH3:52])[CH3:51])[C:41]=1[NH:40][CH2:39][C:37]1[N:38]=[C:33]([C:21]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:22]=2[CH:14]([NH:13][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:15][CH2:16]3)[CH:34]=[CH:35][CH:36]=1)([CH3:48])[CH3:49]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 90311811N-[(6-Bromopyridin-2-yl)methyl]-2,6-diisopropylanilineHCID 123849583N-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-amine

Product 1

HCID 1180726027-(6-(((2,6-diisopropylphenyl)amino)methyl)pyridin-2-yl)-N-phenyl-2,3-dihydro-1H-inden-1-amine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 2.21 g (21.0 mmol) of Na2CO3 in a mixture of 80 ml of water and 25 ml of methanol was purged with argon for 30 min. The obtained solution was added to a mixture of 2.80 g (8.40 mmol) of N-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-amine, 2.90 g (8.40 mmol) of N-[(6-bromopyridin-2-yl)methyl]-2,6-diisopropylaniline, 0.48 g (0.40 mmol) of Pd(PPh3)4, and 120 ml of toluene. This mixture was stirred for 12 h at 70° C., 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=100:5:1, vol.). Yield 2.00 g (50%) of a yellow oil. Anal. calc. For C33H37N3: C, 83.33; H, 7.84; N, 8.83. Found: C, 83.49; H, 7.66; N, 8.65. 1H NMR (CDCl3): δ 7.56-7.61 (m, 3H, 6-H in indane and 4.5-H in Py); 7.46-7.51 (m, 2H, 3,5-H in phenyl); 7.14-7.16 (m, 1H, 4-H in indane); 7.08-7.12 (m, 5H, 3-H in Py, 3,4,5-H in 2,6-diisopropylphenyl and 5-H in indane); 6.65 (m, 1H, 4-H in phenyl); 6.53 (m, 2H, 2,6-H in phenyl); 5.21-5.22 (m, 1H, 1-H in indane); 3.95-4.15 (m, 4H, CH2NH and NH-phenyl and NH-2,6-diisopropylphenyl); 3.31 (sept, J=6.8 Hz, 2H, CH in 2,6-diisopropylphenyl); 3.16-3.24 (m, 1H, 3- or 3′-H in indane); 2.91-2.97 (m, 1H, 3′- or 3-H in indane); 2.21-2.37 (m, 2H, 2,2′-H in indane); 1.19-2.21 (m, 12H, CH3 in 2,6-diisopropylaniline).

Workup

  1. customwas purged with argon for 30 min
  2. temperaturecooled to room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with 3×50 ml of ethyl acetate
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated to dryness
  9. customThe residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate-triethylamine=100:5:1, vol.)

Sources & evidence

ORD record
ord-85237ddb346947458ea7d8755e77ae12
Source dataset
uspto-grants-2016_04
Patent number
US09315593B2

Reaction notes

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