4-Methylmorpholine → HCID 58827249, compound

HRID 448415Notes

Reaction equation

HRID 448415 reaction equation
CN1CCOCC1.[O:8]=[C:9]1[CH:14]([N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3[NH:25][CH2:26][C:27](O)=[O:28])[C:16]2=[O:30])[CH2:13][CH2:12][C:11](=[O:31])[NH:10]1.ClC(OCC)=O.[CH:38]1([NH2:41])[CH2:40][CH2:39]1>C1COCC1>[CH:38]1([NH:41][C:27](=[O:28])[CH2:26][NH:25][C:21]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:22]=2[C:23](=[O:24])[N:15]([CH:14]2[CH2:13][CH2:12][C:11](=[O:31])[NH:10][C:9]2=[O:8])[C:16]3=[O:30])[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 69828CyclopropylamineHCID 58827328N-[2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]glycine

Product 1

HCID 58827249HCID 58827249, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Methylmorpholine (0.15 g, 1.5 mmol) was added to a stirred suspension of [2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylamino]acetic acid (0.50 g, 1.5 mmol) in 50 mL THF under nitrogen at room temperature. Ethyl chloroformate (0.16 g, 1.5 mmol) was then added. Following 30 minutes stirring at room temperature, cyclopropylamine (0.086 g, 1.5 mmol) was added, and stirring proceeded for 21 hours. The solvent was evaporated in vacuo, and the dark yellow residue was dissolved in ethyl acetate (200 mL) and washed with sat. sodium bicarbonate (2×100 mL), water (100 mL), 1N citric acid (2×100 mL), water (100 mL) and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to provide 0.15 g (27%) of the product as a yellow solid: mp 240-242° C.; 1H NMR (DMSO-d6) δ 0.39-0.45 (m, 2H), 0.59-0.73 (m, 2H), 2.02-2.06 (m, 1H), 2.45-2.70 (m, 3H), 2.96-2.83 (m, 1H), 3.88 (d, J=5.3 Hz, 2H), 5.07 (dd, J=12.5 Hz, J=5.3 Hz, 1H), 6.83-6.92 (m, 2H), 7.07 (d, J=7.0 Hz, 1H), 7.60 (t, J=7.9 Hz, 1H), 11.11 (s, 1H); 13C NMR (DMSO-d6) δ 5.57, 22.13, 22.26, 30.96, 44.92, 48.59, 109.77, 110.88, 117.42, 132.02, 136.17, 145.80, 167.28, 168.68, 169.46, 170.07, 172.77; Anal. calcd. for C18H18N4O5: C, 58.37; H, 4.90; N, 15.13. Found: C, 58.16; H, 4.64; N, 14.84.

Workup

  1. stirringstirring
  2. waitproceeded for 21 hours
  3. customThe solvent was evaporated in vacuo
  4. dissolutionthe dark yellow residue was dissolved in ethyl acetate (200 mL)
  5. washwashed with sat. sodium bicarbonate (2×100 mL), water (100 mL), 1N citric acid (2×100 mL), water (100 mL) and brine (100 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-8317c6da012342808c221f6ecfc3e73a
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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