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

HRID 1171424Notes

Reaction equation

HRID 1171424 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.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:41][C:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45]([NH2:52])=[CH:44][CH:43]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[Br:41][C:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45]([NH:52][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:44][CH:43]=1

Participants

7

Reactant 4

HCID 753034-Bromo-1-naphthylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222381233-Fluoro-5-(morpholin-4-yl)benzoic acid

Product 1

HCID 59553247N-(4-bromo-naphthalen-1-yl)-3-fluoro-5-morpholin-4-yl-benzamideYield 21.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Fluoro-5-morpholin-4-yl-benzoic acid (4.45 g, 19.8 mmol) and HBTU (8.19 g, 21.6 mmol) are stirred at room temperature in dry DMF (40 ml) for 1 hour. 4-Bromo-naphthalen-1-ylamine (4.0 g, 18.0 mmol) and diisopropylethylamine (4.8 ml, 27 mmol) are then added and the mixture is stirred at room temperature for 16 hours. The mixture is poured into ethyl acetate (300 ml) and washed with water (250 ml). The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is crystallized from ethyl acetate and hexanes to give N-(4-bromo-naphthalen-1-yl)-3-fluoro-5-morpholin-4-yl-benzamide as a pink powder (1.688 g). Mp: 195-6° C. 1H NMR 300 MHz (DMSO-d6) δ 10.5 (s, 1H), 8.19 (d, 1H, J=6 Hz), 8.04 (d, 1H, J=8.4 Hz), 7.94 (d, 1H, J=8.4 Hz), 7.71 (m, 2H), 7.53 (d, 1H, J=8.1Hz), 7.47 (s, 1H), 7.25 (d, 1H, J=8.4 Hz), 7.05 (d, 1H, J=12.3 Hz), 3.76 (s, 4H), 3.26 (s, 4H). MS: 429 (M+1).

Workup

  1. washwashed with water (250 ml)
  2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is crystallized from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-e3ca3355b90543dab770b1eb826401bb
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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