Dimethylformamide → HCID 178426519, compound

HRID 588028Notes

Reaction equation

HRID 588028 reaction equation
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.C1(O[C:33](=O)[NH:34][C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[C:37]([Cl:42])[CH:36]=2)C=CC=CC=1.CC[N:46]([CH:50](C)C)C(C)C.C[N:54](C=O)C>>[Cl:42][C:37]1[CH:36]=[C:35]([N:34]=[C:33]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)[NH:54][C:50]#[N:46])[CH:40]=[CH:39][C:38]=1[CH3:41]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 4164583HCID 4164583, compoundHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Product 1

HCID 178426519HCID 178426519, compoundYield 17%

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonic acid salt (0.18 g, 0.5 mmol) in DMF (2 mL), was added (3-chloro-4-methyl-phenyl)-carbamic acid phenyl ester (143 mg, 0.5 mmol) and DIPEA (83 μL, 0.5 mmol). The mixture was stirred at 100° C. for 4 hours. The mixture was concentrated under reduced pressure to remove DMF, purified on silica gel column eluted using methanol and methylene chloride to give N″-(3-Chloro-4-methyl-phenyl)-N′-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-N-cyano-guanidine as a white solid (40 mg, 17% yield). HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 50/50, CH3CN/0.1% H3PO4: tR=3.06 min (96.5%); mp: 325-327 0C.; 1H NMR (DMSO-d6) δ 1.93-2.09 (m, 1H, CHH), 2.25-2.32 (m, 3H, CH3), 2.33-2.45 (m, 1H, CHH), 2.55-2.67 (m, 1H, CHH), 2.82-3.01 (m, 1H, CHH), 4.27-4.57 (m, 4H, CH2, CH2), 5.11 (dd, J=5.1, 13.2 Hz, H, NCH), 7.13 (dd, J=2.3, 8.1 Hz, 1H, Ar), 7.32 (d, J=1.5 Hz, 2H, Ar), 7.43 (d, J=7.7 Hz, 1H, Ar), 7.51 (s, 1H, Ar), 7.71 (d, J=7.7 Hz, 1H, Ar), 7.85 (s, 1H, NH), 9.20 (s, 1H, NH), 10.99 (s, 1H, NH). 13C NMR (DMSO-d6) δ 18.98, 22.49, 31.20, 44.70, 47.15, 51.58, 116.88, 121.98, 122.94, 124.33, 126.97, 130.52, 131.41, 132.08, 133.10, 136.46, 142.36, 142.97, 158.15, 167.86, 170.98, 172.86; LC-MS: 465; Anal Calcd for C23H21ClN6O3+0.6H2O+0.2 EtOAc: C, 57.94: H, 4.86; N, 17.03. Found: C, 57.66; H, 4.81; N, 17.10.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customto remove DMF
  3. custompurified on silica gel column
  4. washeluted

Sources & evidence

ORD record
ord-79065addab384d368f2f34472a67aad4
Source dataset
uspto-grants-2016_01
Patent number
US09227954B2

Reaction notes

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