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

HRID 1641264Notes

Reaction equation

HRID 1641264 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 recrystalized 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=5.1 Hz, 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 recrystalized from EtOH (50 ml)

Sources & evidence

ORD record
ord-3fdd7fa1f0984481889944378d595169
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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