Triethylamine → N-[1-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-6-(1-hydroxy-1-methylethyl)-2-naphthamide

HRID 2425576Notes

Reaction equation

HRID 2425576 reaction equation
[OH:1][C:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH:11]=[C:10]([C:15]([OH:17])=O)[CH:9]=[CH:8]2)([CH3:4])[CH3:3].Cl.Cl.[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([C@H:27]([NH2:29])[CH3:28])[CH:23]=[N:22]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([CH:27]([NH:29][C:15]([C:10]2[CH:9]=[CH:8][C:7]3[C:12](=[CH:13][CH:14]=[C:5]([C:2]([OH:1])([CH3:3])[CH3:4])[CH:6]=3)[CH:11]=2)=[O:17])[CH3:28])[CH:23]=[N:22]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 137823686-(2-Hydroxy-2-propyl)naphthalene-2-carboxylic acidHCID 67180429HCID 67180429, compound

Product 1

HCID 24947119N-[1-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-6-(1-hydroxy-1-methylethyl)-2-naphthamideYield 58.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF (3 ml) solution of 6-(1-Hydroxy-1-methyl-ethyl)-naphthalene-2-carboxylic acid (U.S. Pat. No. 4,638,087, published 20 Jan. 1987, 95 mg, 0.413 mmol), Amine 9 (1-(5-Methyl-1H-pyrazol-4-yl)ethanamine dihydrochloride, 95 mg, 0.352 mmol), HBTU (188 mg, 0.495 mmol) and triethylamine (0.173 ml, 1.24 mmol) were added and the mixture was stirred for 24 hours at room temperature. The reaction was quenched with sat. NaHCO3 aq and water, and the product extracted with EtOAc 3 times. The combined organic extracts were dried over Na2SO4, and concentrated in vacuo. The crude material was purified by silica gel column chromatography (Ethylacetate:Hexane=2:1) to give the title product as a white solid (84.4 mg, 58.2% yield). 1H NMR (300 MHz, DMSO-d6) δ 1.46-1.49 (3H, d), 1.50-1.53 (6H, s) 2.22-2.24 (3H, s) 3.67-3.68 (3H s) 5.13-5.20 (2H, m) 7.38-7.39 (1H, s) 7.69-7.72 (1H, d) 7.81-8.00 (4H, m) 8.39-8.40 (1H, s) 8.68-8.72 (1H, d). MS (ESI) m/z 352 (M+H)+.

Workup

  1. customThe reaction was quenched with sat. NaHCO3 aq and water
  2. extractionthe product extracted with EtOAc 3 times
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by silica gel column chromatography (Ethylacetate:Hexane=2:1)

Sources & evidence

ORD record
ord-c8b6407c872249a89a1cf6cf9f6aaefe
Source dataset
uspto-grants-2011_06
Patent number
US07964732B2

Reaction notes

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