Triethylamine → 1,1-Dimethylethyl 9-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 1514245Notes

Reaction equation

HRID 1514245 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:10]=[C:11]([C:19]([OH:21])=O)[CH:12]=[N:13][C:14]=1[O:15][CH:16]([CH3:18])[CH3:17].O.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.O[NH:46][C:47](=[NH:66])[C:48]1[C:58]2[O:57][CH2:56][CH2:55][N:54]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:53][C:52]=2[CH:51]=[CH:50][CH:49]=1>CN(C)C=O.C(OCC)(=O)C>[Cl:8][C:9]1[CH:10]=[C:11]([C:19]2[O:21][N:46]=[C:47]([C:48]3[C:58]4[O:57][CH2:56][CH2:55][N:54]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:53][C:52]=4[CH:51]=[CH:50][CH:49]=3)[N:66]=2)[CH:12]=[N:13][C:14]=1[O:15][CH:16]([CH3:17])[CH3:18]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178452412HCID 178452412, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 594034701,1-Dimethylethyl 9-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Triethylamine (0.281 ml, 2.02 mmol) was added to a stirred solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (may be prepared as described in WO9702244; 217 mg, 1.01 mmol) in N,N-dimethylformamide (20 ml) followed by hydroxybenzotriazole hydrate (185 mg, 1.21 mmol) then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (232 mg, 1.21 mmol) and lastly 1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (Preparation 65) (310 mg, 1.009 mmol). The reaction mixture was heated to 60° C. for 48 hours, then allowed to cool before diluting with ethyl acetate and washing with water. The organic phase was dried and evaporated. Purification of the residue by column chromatography, eluting with 15-25% ethyl acetate in cyclohexane to give the title compound as an amber coloured gum (280 mg).

Workup

  1. temperatureto cool
  2. washwashing with water
  3. customThe organic phase was dried
  4. customevaporated
  5. customPurification of the residue by column chromatography
  6. washeluting with 15-25% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-f8572d34488d45638b8d9da298115f82
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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