3-Bromobenzoic acid → 3-bromo-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide

HRID 1171264Notes

Reaction equation

HRID 1171264 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH2:20])=[CH:12][CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Br:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25](O)=[O:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25]([NH:20][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([O:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:11][CH:12]=1)=[O:26]

Participants

6

Reactant 4

HCID 114563-Bromobenzoic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110439124-(2-Morpholinoethoxy)naphthalen-1-amine

Product 1

HCID 595531183-bromo-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamideYield 50.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 40 ml vial is added 4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-amine (1.5 g, 5.50 mmol), 3-bromobenzoic acid (1.66 g, 8.2 mmol), HBTU (3.13 g, 8.2 mmol) and Hunig's base (2.0 ml, 11.0 mmol). The mixture is dissolved in DMF (10 ml), flushed with argon, sealed and agitated at room temperature for 8 hrs. The crude mixture is diluted with water (100 ml) and partitioned with EtOAc (100 ml). The organic layer is washed with water (100 ml). The combined aqueous layers are extracted with EtOAc (2×50 ml). The combined organic layers are dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by flash column chromatography (5% MeOH in ethyl acetate) to afford 3-bromo-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide (1.27 g, 48%). MS: 455 (M+1).

Workup

  1. customflushed with argon
  2. customsealed
  3. additionThe crude mixture is diluted with water (100 ml)
  4. custompartitioned with EtOAc (100 ml)
  5. washThe organic layer is washed with water (100 ml)
  6. extractionThe combined aqueous layers are extracted with EtOAc (2×50 ml)
  7. dry with materialThe combined organic layers are dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by flash column chromatography (5% MeOH in ethyl acetate)

Sources & evidence

ORD record
ord-e48240eb1ac44a32b5a376c51c809b4f
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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