N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropyl]hydrazide

HRID 1974515Notes

Reaction equation

HRID 1974515 reaction equation
[CH3:1][C:2]([CH3:13])([O:4][C:5]([NH:7][CH2:8][CH2:9][C:10]([OH:12])=O)=[O:6])[CH3:3].ClC1C=CC2OC3C=CC=CC=3CN(C(O)=O)C=2C=1.[Cl:33][C:34]1[CH:52]=[CH:51][C:37]2[O:38][C:39]3[CH:50]=[CH:49][CH:48]=[CH:47][C:40]=3[CH2:41][N:42]([C:43]([NH:45][NH2:46])=[O:44])[C:36]=2[CH:35]=1.CCN(C(C)C)C(C)C.OS([O-])(=O)=O.[K+]>CN(C=O)C.CCOC(C)=O>[CH3:13][C:2]([CH3:1])([O:4][C:5]([NH:7][CH2:8][CH2:9][C:10]([NH:46][NH:45][C:43]([N:42]1[CH2:41][C:40]2[CH:47]=[CH:48][CH:49]=[CH:50][C:39]=2[O:38][C:37]2[CH:51]=[CH:52][C:34]([Cl:33])=[CH:35][C:36]1=2)=[O:44])=[O:12])=[O:6])[CH3:3]

Participants

8

Reactant 5

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 135604618-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, hydrazideHCID 219834678-chlorodibenz[b,f][1,4]oxazepine-10(11H)carboxylic acid

Product 1

HCID 152373958-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropyl]hydrazideYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of 3.78 g (20 mmol) of N-[(1,1-dimethylethoxy)carbonyl]-β-alanine (6), prepared as described above in Example 6, and 5.79 (20 mmol) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)carboxylic acid, hydrazine (1), prepared as described above in Example 1, in 50 mL of DMF cooled in an icebath was added 3.5 mL (20 mmol) of DIEA followed by 4.22 g (22 mmol) of N,N-dimethylaminopropylethylcarbodiimide hydrochloride. The reaction was allowed to warm to ambient temperature over a period of 16 hours. To the reaction mixture was added 100 mL of EtOAc and 200 mL of M KHSO4. The layers were separated and then the organic layer was washed with 2×100 mL of M KHSO4, 2×100 mL of a saturated KHCO3 solution, and 100 mL of brine. The organic layer was dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The resulting product was purified by column chromatography to yield 4.75 g (52%) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropyl]hydrazide (7). Analysis calculated for C22H25N4O5Cl.0.75 H2O (M.W. 474.43): C, 55.70; H, 5.63; N, 11.81. Found: C, 55.42; H, 5.76; N, 12.11.

Workup

  1. customprepared
  2. temperaturecooled in an icebath
  3. customThe layers were separated
  4. washthe organic layer was washed with 2×100 mL of M KHSO4, 2×100 mL of a saturated KHCO3 solution, and 100 mL of brine
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting product was purified by column chromatography

Sources & evidence

ORD record
ord-31cac2b75e164d948b08cb3521e110da
Source dataset
uspto-grants-1994_02
Patent number
US05283240

Reaction notes

Loading…