Diisopropylethylamine → 2-{4-[5-(2-Diethylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethanol

HRID 2069428Notes

Reaction equation

HRID 2069428 reaction equation
[CH2:1]([N:3]([CH2:14][CH3:15])[C:4]1[N:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[C:6]([CH3:13])[N:5]=1)[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.O[NH:48][C:49](=[NH:59])[C:50]1[CH:55]=[CH:54][C:53]([CH2:56][CH2:57][OH:58])=[CH:52][CH:51]=1>CN(C=O)C.CCOC(C)=O.O1CCOCC1>[CH2:14]([N:3]([CH2:1][CH3:2])[C:4]1[N:9]=[C:8]([C:10]2[O:12][N:59]=[C:49]([C:50]3[CH:55]=[CH:54][C:53]([CH2:56][CH2:57][OH:58])=[CH:52][CH:51]=3)[N:48]=2)[CH:7]=[C:6]([CH3:13])[N:5]=1)[CH3:15]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 242773182-(Diethylamino)-6-methylpyrimidine-4-carboxylic acidHCID 59604233CID 59604233

Product 1

HCID 685054582-{4-[5-(2-Diethylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethanolYield 58.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-diethylamino-6-methylpyrimidine-4-carboxylic acid (1.31 g, 6.28 mmol) in DMF (20 mL) is added DIPEA (3.23 mL, 18.8 mmol) followed by TBTU (2.62 g, 8.17 mmol). The mixture is stirred at rt for 10 min before N-hydroxy-4-(2-hydroxy-ethyl)-benzamidine (1.24 g, 6.91 mmol) is added. After stirring for 1 h, the reaction mixture is diluted with EtOAc and the solution is washed with sat. aq. NaHCO3. The aq. phase is extracted with EtOAc and the combined org. extracts are dried over MgSO4, filtered and concentrated to give the crude hydroxyamidine ester intermediate (3.56 g). This material is dissolved in dioxane (50 mL) and the resulting solution is stirred at 85° C. for 16 h. The solvent is evaporated and the crude product is purified by CC (eluting with EtOAc/Heptane 1:4) to give 2-{4-[5-(2-diethylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethanol as a yellow solid (1.30 g); LC-MS: tR=1.07 min; [M+H]+=354.07. 1H NMR (CDCl3): δ 1.25 (t, J=7.0 Hz, 6H), 1.45 (m, 1H), 2.47 (s, 3H), 2.98 (t, J=6.5 Hz, 2H), 3.75 (q, J=7.0 Hz, 4H), 3.95 (m, 2H), 7.23 (s, 1H), 7.41 (d, J=7.8 Hz, 2H), 8.15 (d, J=7.5 Hz, 2H).

Workup

  1. additionis added
  2. washthe solution is washed with sat. aq. NaHCO3
  3. extractionThe aq. phase is extracted with EtOAc
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude hydroxyamidine ester intermediate (3.56 g)
  8. stirringthe resulting solution is stirred at 85° C. for 16 h
  9. customThe solvent is evaporated
  10. customthe crude product is purified by CC (eluting with EtOAc/Heptane 1:4)

Sources & evidence

ORD record
ord-719c55a66cdd4d2aae8c69664107398c
Source dataset
uspto-grants-2012_10
Patent number
US08299086B2

Reaction notes

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