Diisopropylethylamine → HCID 59553324, compound

HRID 1171403Notes

Reaction equation

HRID 1171403 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[CH2:16][CH2:15][CH:14]([CH3:17])[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.C(N(C(C)C)CC)(C)C.[CH3:51][O:52][C:53](=[O:67])[CH2:54][O:55][C:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:59]([NH2:66])=[CH:58][CH:57]=1>CN(C)C=O.O>[CH3:51][O:52][C:53](=[O:67])[CH2:54][O:55][C:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:59]([NH:66][C:5](=[O:7])[C:4]2[CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][CH:14]([CH3:17])[CH2:13][CH2:12]3)[CH:10]=[C:2]([F:1])[CH:3]=2)=[CH:58][CH:57]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59553142Methyl 2-((4-aminonaphthalen-1-yl)oxy)acetateHCID 595533113-Fluoro-5-(4-methylpiperidin-1-yl)benzoic acid

Product 1

HCID 59553324HCID 59553324, compoundYield 82.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-fluoro-5-(4-methylpiperidin-1-yl)-benzoic acid (0.650 g, 2.7 mmol) in dimethylformamide (5 ml) is treated with HBTU (1.7 g, 1.7 eq) and diisopropylethylamine (1.6 ml, 3.5 eq). The mixture is stirred for five minutes at room temperature before a solution of (4-aminonaphthalen-1-yloxy)-acetic acid methyl ester (0.696 g, 1.1 eq) in DMF (2 ml) is added. The mixture is then stirred at room temperature for an additional 15 h before being diluted with water and extracted with ethyl acetate. The organic layer is washed with water, dried over Na2SO4 and evaporated to dryness. The residue is purified by column chromatography on silica gel, eluted with ethyl acetate in hexane (10-30%) to give {4-[3-fluoro-5-(4-methylpiperidin-1-yl)-benzoylamino]-naphthalen-1-yloxy}-acetic acid methyl ester as a solid (1.0 g). Mp: 50-51° C. 1H NMR (300 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.26 (m, 1H), 7.87 (m, 1H), 7.58 (m, 2H), 7.41 (m, 2H), 7.14 (d, J=8.7 Hz, 1H), 6.96 (m, 3H), 5.05 (s, 2H), 3.84 (d, J=12.6 Hz, 1H), 3.74 (s, 3H) 2.77 (t, J=11.7 Hz, 2H), 1.68 (brd, 2H), 1.60 (m, 1H), 1.20 (m, 2H), 0.94 (d, J=6.3 Hz, 3H). MS: 451 (M+1).

Workup

  1. additionis added
  2. extractionextracted with ethyl acetate
  3. washThe organic layer is washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customThe residue is purified by column chromatography on silica gel
  7. washeluted with ethyl acetate in hexane (10-30%)

Sources & evidence

ORD record
ord-bacba5a0b8dc444483fde27cef48d691
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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