Toluene → HCID 71289517, compound

HRID 717538Notes

Reaction equation

HRID 717538 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[C:10]([NH:13][C:14]([NH:16]C3C=CC=CC=3)=[O:15])[CH:11]=[CH:12][C:6]=2[N:5]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:24]=2)[CH2:3]1.[C:38]1([CH3:44])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.Br[C:46]1[CH:51]=[C:50]([CH3:52])[N:49]=[C:48]([CH3:53])[CH:47]=1.[F-].[Cs+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:44]([NH:16][C:14]([NH:13][C:10]1[CH:11]=[CH:12][C:6]2[N:5]=[C:4]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:46]4[CH:51]=[C:50]([CH3:52])[N:49]=[C:48]([CH3:53])[CH:47]=4)[CH:24]=3)[CH2:3][C:2](=[O:1])[NH:8][C:7]=2[CH:9]=1)=[O:15])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 25953Cesium fluorideHCID 130817354-Bromo-2,6-dimethylpyridineHCID 71289637HCID 71289637, compound

Product 1

HCID 71289517HCID 71289517, compoundYield 10.16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 1 (60 mg, 0.12 mmol) in THF:toluene (10 mL, 1:1) were added 4-bromo-2,6-dimethylpyridine (22 mg, 0.12 mmol) and CsF (54 mg, 0.36 mmol) at RT under inert atmosphere and degassed for 15 min in argon atmosphere. To the resulting solution was added Pd(dppf)2Cl2 (8.0 mg, 0.012 mmol) at RT and again degassed for another 10 min. The resulting reaction mixture was heated to 80° C. and stirred for 12 h; progress of the reaction was monitored by TLC. The reaction mixture was allowed to cool to RT and concentrated under reduced pressure to obtain the crude. The crude material was purified by silica gel column chromatography (eluent: 5% MeOH/CH2Cl2) to afford the title compound 92 (6.0 mg, 10.16%) as yellow solid. 1H NMR (500 MHz, DMSO-d6): δ 10.50 (bs, 1H), 9.64 (bs, 1H), 8.78 (bs, 1H), 8.31 (s, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.63 (t, J=8.0 Hz, 1H), 7.42 (s, 2H), 7.38-7.31 (m, 3H), 7.25-7.23 (m, 5H), 6.64 (t, J=6.0 Hz, 1H), 4.31 (d, J=6.0 Hz, 2H), 3.56 (s, 2H), 2.49 (s, 6H). LCMS: m/z 490 [M+1]+

Workup

  1. customdegassed for 15 min in argon atmosphere
  2. customagain degassed for another 10 min
  3. customThe resulting reaction mixture
  4. temperatureto cool to RT
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude
  7. customThe crude material was purified by silica gel column chromatography (eluent: 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-05a2c4b24c114e35bc0a42b2f498e5c6
Source dataset
uspto-grants-2015_11
Patent number
US09193710B2

Reaction notes

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