Formate → HCID 178503849, compound

HRID 1499307Notes

Reaction equation

HRID 1499307 reaction equation
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([S:19][CH3:20])[O:7][C@H:6]1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][NH2:38])=[CH:31][CH:30]=2)[CH:22]=1)(=O)C.[N+]([O-])(O)=O.CC1C=C(C)[N:46]([C:50](=N)[NH2:51])N=1.CCN(C(C)C)C(C)C.C([O-])=O>CC#N>[CH3:27][C:24]1[CH:25]=[CH:26][C:21]([C@H:6]2[C@H:5]([OH:4])[C@@H:10]([OH:11])[C@H:9]([OH:15])[C@@H:8]([S:19][CH3:20])[O:7]2)=[CH:22][C:23]=1[CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH2:37][NH:38][C:50]([NH2:51])=[NH:46])=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 283FormateHCID 81531DiisopropylethylamineHCID 1981863,5-Dimethyl-1H-pyrazole-1-carboxamidine mononitrateHCID 90177060HCID 90177060, compound

Product 1

HCID 178503849HCID 178503849, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (2S,3S,4R,5S,6R)-2-(3-(4-(2-aminoethoxy)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (44, 31 mg, 0.057 mmol) and 3,5-dimethyl-1H-pyrazole-1-carboximidamide nitrate (23 mg, 0.11 mmol) in CH3CN was added DIPEA (30 μL, 0.17 mmol). The reaction was heated at 60° C. for 4 hours, then cooled to room temperature and concentrated under vacuum. The residue was dissolved in MeOH and treated with a few drops of NaOMe (25 wt % in MeOH) for 1 hour. The reaction was concentrated under vacuum, and the residue was purified by prep HPLC (C18 30×100 mm column, 5-40% CH3CN/10 mM aqueous ammonium formate, 45 mL/min) to give urea 46 (9 mg, 34% yield) as the formate salt. 1H NMR (400 MHz, MeOH-d4) δ ppm 7.11-7.20 (m, 3 H), 7.07 (d, J=8.6 Hz, 2 H), 6.81-6.89 (m, 2 H), 4.39 (d, J=9.3 Hz, 1 H), 4.12 (d, J=9.1 Hz, 1 H), 4.08 (t, J=4.9 Hz, 2 H), 3.94 (s, 2 H), 3.58 (t, J=5.1 Hz, 2 H), 3.34-3.48 (m, 3 H), 2.20 (s, 3 H), 2.14 (s, 3 H); MS (ES+) [M+H]+=462.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under vacuum
  3. dissolutionThe residue was dissolved in MeOH
  4. additiontreated with a few drops of NaOMe (25 wt % in MeOH) for 1 hour
  5. concentrationThe reaction was concentrated under vacuum
  6. customthe residue was purified by prep HPLC (C18 30×100 mm column, 5-40% CH3CN/10 mM aqueous ammonium formate, 45 mL/min)

Sources & evidence

ORD record
ord-093c13a6167b4648af2e9b37464915b4
Source dataset
uspto-grants-2015_12
Patent number
US09200025B2

Reaction notes

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