Diisopropylethylamine → 3-bromo-5-(trifluoromethyl)-N-(3-(1,2-dihydro-1,7-dimethyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl)benzamide

HRID 424709Notes

Reaction equation

HRID 424709 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:48][C:49]1[CH:50]=[CH:51][C:52]([CH3:68])=[C:53]([C:55]2[C:56](=[O:67])[N:57]([CH3:66])[C:58]3[C:63]([CH:64]=2)=[CH:62][N:61]=[C:60]([CH3:65])[CH:59]=3)[CH:54]=1>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([NH:48][C:49]1[CH:50]=[CH:51][C:52]([CH3:68])=[C:53]([C:55]2[C:56](=[O:67])[N:57]([CH3:66])[C:58]3[C:63]([CH:64]=2)=[CH:62][N:61]=[C:60]([CH3:65])[CH:59]=3)[CH:54]=1)=[O:7]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110867883-Bromo-5-(trifluoromethyl)benzoic acidHCID 592123103-(5-amino-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

Product 1

HCID 592125063-bromo-5-(trifluoromethyl)-N-(3-(1,2-dihydro-1,7-dimethyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-5-trifluoromethyl-benzoic acid 21 (193 mg, 0.716 mmol) in DMF (5 mL) is added HATU (272 mg, 0.716 mmol) and di-isopropylethylamine (278 mg, 2.15 mmol) at rt. The resulting mixture is stirred for 2 min. A solution of 3-(5-amino-2-methyl-phenyl)-1,7-dimethyl-1H-[1,6]naphthyridin-2-one 15 (200 mg, 0.716 mmol) in DMF (5 mL) is added. The reaction mixture is stirred at rt overnight, diluted with EtOAc, and washed with brine three times. The organic layer is dried (MgSO4) and concentrated. The residue is purified by automated chromatography to give the desired product 22 as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.50 (s, 1H), 8.99 (s, 1H), 8.38 (s, 1H), 8.22 (s, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.72 (s, 1H), 7.66 (d, J=2.1 Hz, 1H), 7.62 (dd, J=8.3, 2.2 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 3.63 (s, 3H), 2.65 (s, 3H), 2.08 (s, 3H).

Workup

  1. stirringThe reaction mixture is stirred at rt overnight
  2. washwashed with brine three times
  3. dry with materialThe organic layer is dried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue is purified by automated chromatography

Sources & evidence

ORD record
ord-8f209b408693453584a4718fc89d1d42
Source dataset
uspto-grants-2012_01
Patent number
US08106068B2

Reaction notes

Loading…