1,2-Dichloroethane → HCID 59403458, compound

HRID 1514181Notes

Reaction equation

HRID 1514181 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([OH:8])=O)#[N:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O[NH:31][C:32](=[NH:51])[C:33]1[CH:34]=[CH:35][C:36]2[CH2:42][N:41]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:40][CH2:39][CH2:38][C:37]=2[CH:50]=1>CN(C=O)C.CCOC(C)=O.CCCCCC.CCOC(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:31]=[C:32]([C:33]3[CH:34]=[CH:35][C:36]4[CH2:42][N:41]([C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH2:40][CH2:39][CH2:38][C:37]=4[CH:50]=3)[N:51]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

8

Reactant 4

HCID 111,2-Dichloroethane2×HCID 757711-HydroxybenzotriazoleHCID 21956832RP-1011242×HCID 178451749HCID 178451749, compound2×

Product 1

HCID 59403458HCID 59403458, compoundYield 45.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

3-Cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (302 mg, 1.474 mmol), EDC (339 mg, 1.768 mmol) and HOBT (271 mg, 1.768 mmol) were stirred in DMF (3 ml) for 5 minutes. 1,1-Dimethylethyl 7-[(hydroxyamino)(imino)methyl]-1,3,4,5-tetrahydro-2H-2-benzazepine-2-carboxylate (Preparation 5) (450 mg, 1.474 mmol) was added and the reaction mixture stirred at RT for 1 hour. There was still some 3-cyano-4-[(1-methylethyl)oxy]benzoic acid acid present. Further quantities of EDC (100 mg) and 1,1-Dimethylethyl 7-[(hydroxyamino)(imino)methyl]-1,3,4,5-tetrahydro-2H-2-benzazepine-2-carboxylate (100 mg) were added and the reaction stirred for 1 hour. Then the reaction was heated at 80° C. for 3 hours and left standing overnight. The reaction was then heated at 90° C. for 1 hour. EtOAc (70 ml) was added and the reaction mixture washed with sat. NaHCO3 (50 ml) and water (2×70 ml), dried over anhydrous MgSO4 and evaporated. The crude material obtained was subjected to biotage chromatography (EtOAc/hexane 1:2), yielding a white solid on evaporation. Trituration with ether yielded the title compound (320 mg) as a white solid. NMR (400 MHz, d6DMSO) 1.31 (9H, s), 1.38 (6H, d), 1.69 (2H, br. s), 3.06 (2H, broad s), 3.65 (2H, br. s), 4.44 (2H, s), 4.94-5.03 (1H, m), 7.38-7.43 (1H, m), 7.56 (1H, d), 7.84-7.91 (2H, m), 8.40 (1H, dd), 8.50 (1H, d)

Workup

  1. stirringthe reaction stirred for 1 hour
  2. temperatureThen the reaction was heated at 80° C. for 3 hours
  3. waitleft
  4. waitstanding overnight
  5. temperatureThe reaction was then heated at 90° C. for 1 hour
  6. washthe reaction mixture washed with sat. NaHCO3 (50 ml) and water (2×70 ml)
  7. dry with materialdried over anhydrous MgSO4
  8. customevaporated
  9. customThe crude material obtained
  10. customyielding a white solid
  11. customon evaporation

Sources & evidence

ORD record
ord-cb7852b6bf0041a9b690c3d3aa5c8252
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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