Diisopropylethylamine → 3-fluoro-5-morpholin-4-yl-N-[4-(2-morpholin-4-yl-ethylamino)-naphthalen-1-yl]-benzamide

HRID 1641277Notes

Reaction equation

HRID 1641277 reaction equation
[N:1]1([CH2:7][CH2:8][NH: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.[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[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.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[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]([NH: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

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222381233-Fluoro-5-(morpholin-4-yl)benzoic acidHCID 59553181N4-(2-morpholin-4-yl-ethyl)-naphthalene-1,4-diamine

Product 1

HCID 595530683-fluoro-5-morpholin-4-yl-N-[4-(2-morpholin-4-yl-ethylamino)-naphthalen-1-yl]-benzamideYield 21.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N4-(2-morpholin-4-yl-ethyl)-naphthalene-1,4-diamine (190 mg, 701 μmol), 3-fluoro-5-morpholinyl benzoic acid (236 mg, 1.05 mmol), HBTU (531 mg, 1.4 mmol) and diisopropylethylamine (0.37 ml, 2.1 mmol) are stirred at room temperature in dimethylformamide (10 ml) for 12 hours. The mixture is poured into ethyl acetate (100 mL) and washed with water (100 ml). The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 5% methanol in ethyl acetate to give 3-fluoro-5-morpholin-4-yl-N-[4-(2-morpholin-4-yl-ethylamino)-naphthalen-1-yl]-benzamide (72 mg). 1H NMR 300 MHz (CDCl3) 7.7-8.0(m, 3H), 7.4-7.6(m, 3H), 7.3(m, 1H), 7.05(m, 1H), 6.7(m, 1H), 6.6(m, 1H), 5.35(m, 1H), 3.65-4.0(m, 8H), 3.2-3.4(m, 6H), 2.8(m, 2H), 2.4-2.55(m, 4H).

Workup

  1. washwashed with water (100 ml)
  2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is purified by column chromatography on silica gel
  5. washeluted with 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-96e592b9ac84418b9c65af4dce2b00a5
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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