Ethyl Acetate → HCID 89714577, compound

HRID 2273069Notes

Reaction equation

HRID 2273069 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([NH:9][C:10](=[O:45])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:28]3[C:27](=[O:29])[N:26]([CH2:30][CH2:31][C:32](O)=[O:33])[CH2:25][C:24]([CH3:36])([CH3:35])[O:23][C:22]=3[N:21]=[C:20]([N:37]3[CH2:43][CH:42]4[O:44][CH:39]([CH2:40][CH2:41]4)[CH2:38]3)[N:19]=2)=[CH:14][CH:13]=1)[CH3:8].[O-]S([O-])(=O)=O.[Na+].[Na+].C(OCC)(=O)C>C1COCC1>[CH2:7]([NH:9][C:10]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[C:28]3[C:27](=[O:29])[N:26]([CH2:30][CH2:31][CH2:32][OH:33])[CH2:25][C:24]([CH3:36])([CH3:35])[O:23][C:22]=3[N:21]=[C:20]([N:37]3[CH2:43][CH:42]4[O:44][CH:39]([CH2:40][CH2:41]4)[CH2:38]3)[N:19]=2)=[CH:16][CH:17]=1)=[O:45])[CH3:8]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24436Sodium SulfateHCID 21226445Aluminium lithium hydride2×HCID 89714824HCID 89714824, compound

Product 1

HCID 89714577HCID 89714577, compoundYield 24.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

13 mg of lithium aluminium hydride (0.34 mmol) are placed in 5 ml of anhydrous THF. A solution containing 90 mg (0.17 mmol) of 3-[4-[4-(3-ethylureido)phenyl]-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triazabenzocyclohepten-6-yl]propionic acid in 10 ml of THF is added dropwise. The reaction mixture is heated at 66° C. for 18 hours. 72 mg of lithium aluminium hydride (1.89 mmol) are added and the mixture is heated for a further 24 hours at 66° C. The medium is then cooled in an ice-water bath to 4° C. and basified with saturated aqueous Na2SO4 solution. Ethyl acetate is added and the mixture is filtered through Celite, rinsed with ethyl acetate and concentrated. The residue is chromatographed on silica gel with a gradient of MeOH containing 10% aqueous ammonia DCM ranging from 0% to 10%. The solid is rinsed with acetonitrile and then with pentane to give 22 mg of 1-ethyl-3-{4-[6-(3-hydroxypropyl)-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]phenyl}urea.

Workup

  1. additionis added dropwise
  2. temperaturethe mixture is heated for a further 24 hours at 66° C
  3. temperatureThe medium is then cooled in an ice-water bath to 4° C.
  4. filtrationthe mixture is filtered through Celite
  5. washrinsed with ethyl acetate
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel with a gradient of MeOH containing 10% aqueous ammonia DCM ranging from 0% to 10%
  8. washThe solid is rinsed with acetonitrile

Sources & evidence

ORD record
ord-8272d151c7224574b839d4e2f869ae6c
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

Loading…