Methylamine → HCID 58827242, compound

HRID 448412Notes

Reaction equation

HRID 448412 reaction equation
O=C1[CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[NH:18][CH2:19][C:20]([OH:22])=O)[C:9]2=[O:23])[CH2:6][CH2:5][C:4](=[O:24])N1.C1C=CC2N([OH:34])N=NC=2C=1.C1C[CH2:44][N:43]2C(=NCCC2)CC1.[CH3:46][NH2:47]>CN(C=O)C.C(Cl)Cl>[O:34]=[C:46]1[CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[NH:18][CH2:19][C:20]([NH:43][CH3:44])=[O:22])[C:9]2=[O:23])[CH2:6][CH2:5][C:4](=[O:24])[NH:47]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58827328N-[2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]glycine

Product 1

HCID 58827242HCID 58827242, compoundYield 65.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylamino]acetic acid (0.73 g, 2.2 mmol) in DMF (20 mL), were successively added HOBt (0.32 g, 2.4 mmol), DBU (0.38 g, 2.5 mmol), methylamine (0.062 g, 2.0 mmol) and EDC-Cl (0.58 g, 3.0 mmol). The solution was stirred overnight at room temperature. The solvent was evaporated in vacuo, giving a yellow oil. The oil was dissolved in CH2Cl2 (100 mL), washed with water (3×50 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo to give a yellow solid. This material was triturated with diethyl ether for 1 hour and then filtered, and the resulting solid was recrystallized from ethanol, and the recrystallized solid was rinsed with diethyl ether, providing 0.45 g (65%) of the product as a yellow solid: mp 239-241° C.; 1H NMR (DMSO-d6) δ 2.01-2.05 (m, 1H), 2.47-2.56 (m, 2H), 2.62 (d, J=4.5 Hz, 3H), 2.97-2.82 (m, 1H), 3.91 (d, J=5.6 Hz, 2H), 5.07 (dd, J=12.5 Hz, J=5.4 Hz, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.95 (t, J=5.5 Hz, 1H), 7.07 (d, J=7.1 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 8.00 (d, J=4.5 Hz, 1H), 11.10 (s, 1H); 13C NMR (DMSO-d6) δ 22.14, 25.53, 30.95, 45.16, 48.53, 109.87, 110.92, 117.38, 132.02, 136.19, 145.80, 167.28, 168.65, 168.87, 169.99, 172.76; Anal. calcd. for C16H16N4O5.0.15H2O.0.03Et2O: C, 55.44; H, 4.79; N, 16.04. Found: C, 55.31; H, 4.56; N, 15.65.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customgiving a yellow oil
  3. washwashed with water (3×50 mL) and brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvent was evaporated in vacuo
  6. customto give a yellow solid
  7. customThis material was triturated with diethyl ether for 1 hour
  8. filtrationfiltered
  9. customthe resulting solid was recrystallized from ethanol
  10. washthe recrystallized solid was rinsed with diethyl ether

Sources & evidence

ORD record
ord-38f45f945e9e4eb583ca27044b209af5
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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