1,2-Dichloroethane → HCID 68468009, compound

HRID 1514237Notes

Reaction equation

HRID 1514237 reaction equation
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[CH:5]=[CH:6][C:7]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9][C:8]=2[CH:21]=1.[C:23]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[O:34][CH:35]([CH3:37])[CH3:36])[C:28](O)=O)#[N:24].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:23]([C:25]1[CH:26]=[C:27]([C:28]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[CH:6][C:7]4[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:9][C:8]=4[CH:21]=3)[N:22]=2)[CH:31]=[CH:32][C:33]=1[O:34][CH:35]([CH3:36])[CH3:37])#[N:24]

Participants

6

Reactant 4

HCID 111,2-Dichloroethane2×HCID 757711-HydroxybenzotriazoleHCID 21956832RP-1011242×HCID 178452415HCID 178452415, compound

Product 1

HCID 68468009HCID 68468009, compoundYield 31.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 1,1-dimethylethyl 7-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (Preparation 75) (0.84 g, 2.73 mmol), 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (0.617 g, 3.01 mmol), EDC (0.786 g, 4.10 mmol) and HOBT (0.502 g, 3.28 mmol) in DMF (10 ml) was stirred at RT overnight. Additional EDC (0.4 g) was added and the reaction stirred for 3 hours. Then additional 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (0.3 g) was added, the reaction heated at 120° C. for 1 hour and left standing overnight. The reaction mixture was partitioned between EtOAc/water, and the organic layer collected, dried (MgSO4) and evaporated. The resulting crude was purified by flash chromatography eluting with EtOAc/iso-hexane 20-30%. Analysis of the puried fractions by LCMS showed some 3-cyano-4-[(1-methylethyl)oxy]benzoic acid present so sodium bicarbonate and EtOAc was added. The EtOAc layer was separated, dried (MgSO4) and evaporated to give the title compound (410 mg) as a white solid. MS (ES): C26H28N4O5 requires 476; found 421 [M+H−56]+.

Workup

  1. waitleft
  2. waitstanding overnight
  3. customThe reaction mixture was partitioned between EtOAc/water
  4. customthe organic layer collected
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe resulting crude was purified by flash chromatography
  8. washeluting with EtOAc/iso-hexane 20-30%
  9. additionwas added
  10. customThe EtOAc layer was separated
  11. dry with materialdried (MgSO4)
  12. customevaporated

Sources & evidence

ORD record
ord-cc8daa6a891c4d8a8b46612fc9becbcc
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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