Diisopropylethylamine → HCID 44199424, compound

HRID 2037356Notes

Reaction equation

HRID 2037356 reaction equation
[CH2:1]([C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[C:7]([CH3:14])[CH:6]=1)[CH:2]([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:46]([C:48]1[CH:63]=[C:62]([C:64](=[NH:67])[NH:65]O)[CH:61]=[C:60]([CH3:68])[C:49]=1[O:50][CH2:51][C@@H:52]([OH:59])[CH2:53][NH:54][C:55](=[O:58])[CH2:56][OH:57])[CH3:47]>CN(C=O)C.O1CCOCC1>[CH2:46]([C:48]1[CH:63]=[C:62]([C:64]2[N:67]=[C:11]([C:9]3[CH:8]=[C:7]([CH3:14])[CH:6]=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[N:10]=3)[O:13][N:65]=2)[CH:61]=[C:60]([CH3:68])[C:49]=1[O:50][CH2:51][C@@H:52]([OH:59])[CH2:53][NH:54][C:55](=[O:58])[CH2:56][OH:57])[CH3:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58418057HCID 58418057, compoundHCID 178436630HCID 178436630, compound

Product 1

HCID 44199424HCID 44199424, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-isobutyl-4-methyl-pyridine-2-carboxylic acid (100 mg, 0.435 mmol) and DIPEA (169 mg, 1.31 mmol) in DMF (5 mL), TBTU (210 mg, 0.653 mmol) is added at 0° C. The mixture is stirred for 15 min at 0° C. before N—((S)-3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenoxy]-2-hydroxy-propyl)-2-hydroxy-acet-amide (170 mg, 0.522 mmol) is added. Stirring is continued at 0° C. for 1 h. The reaction is quenched by adding water. The mixture is diluted with sat. aq. NaHCO3-solution and extracted with EA and two times with DCM. The combined org. extracts are dried over MgSO4, filtered and concentrated to give the crude hydroxy-amidine ester intermediate. This material is dissolved in dioxane (5 mL) and the mixture is stirred at 80° C. for 24 h. The solvent is evaporated and the crude product is purified on prep. TLC plates with DCM containing 10% of 7 N NH3 in methanol followed by prep. HPLC to give the title compound (21 mg) as a pale yellow oil; LC-MS: tR=1.00 min, [M+H]+=483.26; 1H NMR (CDCl3): δ 0.99 (d, J=6.8 Hz, 6H), 1.29 (t, J=7.5 Hz, 3H), 2.21 (hept, J=6.8 Hz, 1H), 2.36 (s, 3H), 2.48 (s, 3H), 2.72 (q, J=7.5 Hz, 2H), 2.79 (d, J=7.3 Hz, 2H), 3.47-3.55 (m, 1H), 3.74-3.92 (m, 3H), 4.16-4.24 (m, 3H), 7.18 (s, 1H), 7.23 (t br, J=5.8 Hz, 1H), 7.88 (s, 1H), 7.90 (s, 1H), 7.99 (s, 1H).

Workup

  1. additionis added
  2. customThe reaction is quenched
  3. additionby adding water
  4. additionThe mixture is diluted with sat. aq. NaHCO3-solution
  5. extractionextracted with EA and two times with DCM
  6. dry with materialextracts are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude hydroxy-amidine ester intermediate
  10. stirringthe mixture is stirred at 80° C. for 24 h
  11. customThe solvent is evaporated
  12. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-a923a76238184feebb02656d82f34533
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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