5-Bromonicotinamide → HCID 16041930, compound

HRID 545173Notes

Reaction equation

HRID 545173 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([C:15]([N:17]2[CH2:22][CH2:21][C:20]3([CH2:31][C:30](=[O:32])[C:29]4[C:24](=[CH:25][CH:26]=[C:27](B5OC(C)(C)C(C)(C)O5)[CH:28]=4)[O:23]3)[CH2:19][CH2:18]2)=[O:16])[CH:4]=1.Br[C:43]1[CH:44]=[N:45][CH:46]=[C:47]([CH:51]=1)[C:48]([NH2:50])=[O:49].O1CCOCC1>C(Cl)(Cl)Cl.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>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([C:15]([N:17]2[CH2:18][CH2:19][C:20]3([CH2:31][C:30](=[O:32])[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:43]5[CH:44]=[N:45][CH:46]=[C:47]([CH:51]=5)[C:48]([NH2:50])=[O:49])[CH:28]=4)[O:23]3)[CH2:21][CH2:22]2)=[O:16])[CH:4]=1

Participants

6

Reactant 3

HCID 18085-BromonicotinamideHCID 312751,4-DioxaneHCID 57700063HCID 57700063, compound

Product 1

HCID 16041930HCID 16041930, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6212ChloroformSolvent

Procedure

350 mg of 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chroman-2,4′-piperidin]-4-one, 151 mg of 5-bromonicotinamide, 72.5 mg of Pd(PPh3)4 and 1.4 mL of 2M Na2CO3aq were heated with 1,4-dioxane at 100° C. and stirred for 21 hours. The reaction solution was diluted with CHCl3, filtered through Celite, and the filtrate was dried with magnesium sulfate and concentrated. The residue was purified through silica gel thin-layer chromatography (CHCl3/MeOH=9/1) to obtain the intended compound. 1H-NMR (400 MHz, CDCl3) δ: 8.90-9.00 (2H, m), 8.36 (1H, s), 8.15 (1H, s), 7.70-7.80 (2H, m), 7.40-7.55 (11H, m), 7.19 (1H, s), 7.17 (1H, d, J=8.8 Hz), 7.09 (1H, d, J=7.8 Hz), 6.3-6.5 (1H, br), 5.7-6.1 (1H, br), 4.50-4.60 (1H, m), 4.10-4.15 (1H, m), 4.08 (3H, s), 4.03 (3H, s), 3.55-3.70 (1H, m), 3.35-3.50 (1H, m), 2.88 (1H, d, J=16.6 Hz), 2.82 (1H, d, J=16.6 Hz), 2.20-2.30 (1H, m), 2.05-2.15 (1H, m), 1.80-2.05 (2H, m). MS [M+H]+=553.

Workup

  1. filtrationfiltered through Celite
  2. dry with materialthe filtrate was dried with magnesium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified through silica gel thin-layer chromatography (CHCl3/MeOH=9/1)
  5. customto obtain the intended compound

Sources & evidence

ORD record
ord-26a4a27900dc4b0eaca5305d9632b949
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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