Hydrochloric Acid → HCID 178525901, compound

HRID 2188757Notes

Reaction equation

HRID 2188757 reaction equation
[H-].[Na+].[C:3]1([CH2:9][NH:10][C:11]([CH:13]([C:19]([O:21]CC)=O)[C:14]([O:16]CC)=O)=[O:12])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:24]1([N:30]=[C:31]=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[NH2:33][CH2:34][C:35]([OH:37])=[O:36].Cl>O1CCOCC1.C1CCN2C(=NCCC2)CC1>[CH:24]1([N:30]2[C:19]([OH:21])=[C:13]([C:14]([NH:33][CH2:34][C:35]([OH:37])=[O:36])=[O:16])[C:11](=[O:12])[N:10]([CH2:9][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:31]2=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 750GlycineHCID 18502Cyclohexyl isocyanateHCID 24758Sodium hydrideHCID 25241833HCID 25241833, compound

Product 1

HCID 178525901HCID 178525901, compoundYield 7.3%

Reagents, catalysts & solvents 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube containing sodium hydride (60% suspension in oil, 46 mg, 1.15 mmoles) in dioxan (3 mL) was treated with diethyl {[(phenylmethyl)amino]carbonyl}-propanedioate (example 1a, 100 mg, 0.34 mmoles) and stirred under argon until evolution ceased. Cyclohexyl isocyanate (90 uL, 0.7 mmoles) was added and the mixture was heated at 100° C. for 30 minutes in a microwave reactor. Glycine (48 mg, 0.65 mmoles) and DBU (4 drops) was added, the flask re-sealed and heated at 160° C. for 1 hour in a microwave reactor. The mixture was poured into 1 molar hydrochloric acid and extracted with dichloromethane (×3). The combined extracts were washed with 1 molar hydrochloric acid and brine, dried and evaporated to give the crude product. Purification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) gave the title compound (10 mg, 7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.12 (t, J=5.18 Hz, 1 H), 7.23-7.34 (m, 6 H), 4.99 (s, 2 H), 4.65 (t, J=11.62 Hz, 1 H), 4.10 (d, J=5.81 Hz, 2 H), 2.21-2.32 (m, 2 H), 1.78 (d, J=12.63 Hz, 2 H), 1.62 (s, 3 H), 1.22-1.33 (m, 3 H), 1.06-1.17 (m, 1 H)

Workup

  1. customthe flask re-sealed
  2. temperatureheated at 160° C. for 1 hour in a microwave reactor
  3. extractionextracted with dichloromethane (×3)
  4. washThe combined extracts were washed with 1 molar hydrochloric acid and brine
  5. customdried
  6. customevaporated
  7. customto give the crude product
  8. customPurification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%)

Sources & evidence

ORD record
ord-a45a07144e504b6893d6df9f0783e211
Source dataset
uspto-grants-2012_12
Patent number
US08324208B2

Reaction notes

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