Potassium cyanate → HCID 10480478, compound

HRID 658150Notes

Reaction equation

HRID 658150 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:27][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])[CH2:18]2)[CH2:13][CH2:14][NH:15][OH:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[O-:33][C:34]#[N:35].[K+]>O>[NH2:35][C:34]([N:15]([CH2:14][CH2:13][C@@H:12]([N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][C:23]=2[NH:27][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])[CH2:18]1)[C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[OH:16])=[O:33]

Participants

4

Reactant 2

HCID 11378442Potassium cyanateHCID 86595520HCID 86595520, compound

Product 1

HCID 10480478HCID 10480478, compoundYield 55.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a solution of (1R)—N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-3-hydroxyamino-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-isobutyramide (1.3 g, 2.6 mmol) in water (30 mL) was added a solution of potassium cyanate (442 mg, 5.5 g) in water (10 mL) at room temperature. After 1 h, the mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with HCl (1N, 25 mL), brine (25 mL) and dried over MgSO4. The solvent was removed in vacuo and the residue was purified by prep HPLC to give (1R)—N-{2-[3-(N-aminocarbonyl-N-hydroxy-amino)-1-(3-ethoxy-4-methoxy-phenyl)-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-isobutyramide as a white solid (0.70 g, 55% yield): mp: 137-139° C. 1H NMR (DMSO-d6) δ 1.18 (d, J=7 Hz, 6H, 2CH3), 1.31 (t, J=7 Hz, 3H, CH3), 2.25-2.34 (m, 2H, CH2), 2.51-2.66 (m, 1H, CH), 3.22-3.40 (m, 2H, CH2), 3.73 (s, 3H, CH3), 3.95-4.06 (m, 2H, CH2), 4.10 (d, J=18 Hz, 1H, NCHH), 4.55 (d, J=18 Hz, 1H, NCHH), 5.26 (t, J=8 Hz, 1H, NCH), 6.34 (s, 2H, NH2), 6.92-6.98 (m, 3H, Ar), 7.18 (d, J=8 Hz, 1H, Ar), 7.50 (t, J=8 Hz, 1H, Ar), 8.29 (d, J=8 Hz, 1H, Ar), 9.34 (s, 1H, CH), 10.48 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.70, 19.18, 28.73, 35.94, 46.25, 47.22, 52.04, 55.43, 63.76, 111.94, 112.40, 116.55, 117.52, 117.60, 119.58, 131.99, 132.73, 137.12, 142.20, 147.89, 148.43, 161.57, 168.34, 174.93; Anal Calcd for C25H32N4O6+0.9 H2O: C, 59.96; H, 6.80; N, 11.19; H2O, 3.24. Found: C, 60.16; H, 6.58; N, 10.81; H2O, 3.24.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (50 mL)
  2. washThe organic layer was washed with HCl (1N, 25 mL), brine (25 mL)
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-93cb9c3d6f2e4561a9edded0a3a5059d
Source dataset
uspto-grants-2011_12
Patent number
US08076369B2

Reaction notes

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