Diisopropylethylamine → 3-tert-butoxy-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide

HRID 1641237Notes

Reaction equation

HRID 1641237 reaction equation
[C:1]([O:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].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.[N:48]1([CH2:54][CH2:55][O:56][C:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[C:60]([NH2:67])=[CH:59][CH:58]=2)[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1>CN(C)C=O.O>[C:1]([O:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:67][C:60]1[C:61]2[C:66](=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:57]([O:56][CH2:55][CH2:54][N:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)=[CH:58][CH:59]=1)=[O:11])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5865983-(Tert-butoxy)benzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110439124-(2-Morpholinoethoxy)naphthalen-1-amine

Product 1

HCID 595534743-tert-butoxy-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamideYield 42.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-tert-butoxy-benzoic acid (0.15 g, 0.774 mmol) in dimethylformamide (5 ml) is added HBTU (0.44 g, 1.5 eq) followed by the addition of diisopropylethylamine (0.296 ml, 3.0 eq). The mixture is stirred at room temperature for five minutes. A solution of 4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine (0.21 g) in dimethylformamide (2 ml) is then added. This mixture is stirred at room temperature for 15 h, diluted with water and extracted with ethyl acetate. The organic layer is washed with water, dried over Na2SO4 and evaporated. The residue is purified by column chromatography on silica gel (ethyl acetate) to give 3-tert-butoxy-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide (0.146 g). Mp: 50-51° C. 1H NMR (300 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.22 (m, 1H), 7.85 (m, 2H), 7.66 (s, 1H), 7.55 (m, 2H), 7.23 (d, J=7.5 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 4.31 (t, J=5.1 Hz, 2H), 3.61 (t, J=4.2 Hz, 4H), 2.89 (brs, 2H), 2.58 (brs, 4H), 1.35 (s, 9H). MS: 449 (M+1).

Workup

  1. stirringThis mixture is stirred at room temperature for 15 h
  2. extractionextracted with ethyl acetate
  3. washThe organic layer is washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue is purified by column chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-52c4335aff1740cda27500e990a76fd4
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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