Water → N-(4-bromo-naphthalen-1-yl)-3-fluoro-5-morpholin-4-yl-benzamide

HRID 1171396Notes

Reaction equation

HRID 1171396 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:10]=1)[C:5]([OH:7])=O.[Br:17][C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([NH2:28])=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.O>C(Cl)Cl>[Br:17][C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([NH:28][C:5](=[O:7])[C:4]2[CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:10]=[C:2]([F:1])[CH:3]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 753034-Bromo-1-naphthylamineHCID 81531DiisopropylethylamineHCID 222381233-Fluoro-5-(morpholin-4-yl)benzoic acid

Product 1

HCID 59553247N-(4-bromo-naphthalen-1-yl)-3-fluoro-5-morpholin-4-yl-benzamideYield 66.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-fluoro-5-morpholin-4-ylbenzoic acid (1.01 g, 4.4 mmol) in methylenechloride (30 ml) is added DMC (0.908 g, 5.4 mmol) and the mixture is stirred for 10 minutes. To this mixture is added 4-bromonaphthalen-1-amine (1.0 g, 4.50 mmol) and Hunig's base (3.21 ml). The mixture is stirred vigorously overnight at room temperature. The mixture is poured into water (200 ml) and extracted with EtOAc (2×100 ml). The organic layers are combined, dried over Na2SO4, filtered and concentrated. The residue is recrystallized from EtOH (50 ml) to give N-(4-bromo-naphthalen-1-yl)-3-fluoro-5-morpholin-4-yl-benzamide as white crystals (1.26 g, 65%). Mp: 187-189° C. 1H NMR (400 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.18 (d, J=6.3 Hz, 1H), 8.02 (d, J=6.0 Hz, 1H), 7.93 (d, J=5.7 Hz, 1H), 7.72 (t, J=5.1Hz, 1H), 7.67 (t, J=5.4 Hz, 1H), 7.51 (d, J=5.7 Hz, 1H), 7.45 (s, 1H), 7.24 (d, J=6.3 Hz, 1H), 7.04 (d, J=9.3 Hz, 1H), 3.74 (t, J=3.3 Hz, 4H), 3.24 (t, J=3.9 Hz, 4H). MS 429 (M+1).

Workup

  1. stirringThe mixture is stirred vigorously overnight at room temperature
  2. extractionextracted with EtOAc (2×100 ml)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is recrystallized from EtOH (50 ml)

Sources & evidence

ORD record
ord-a4d61b65b3694adab654e36fbd35e987
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

Loading…