Triethylamine → HCID 22103508, compound

HRID 1457204Notes

Reaction equation

HRID 1457204 reaction equation
[CH3:1][C:2]([CH3:12])([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.C(Cl)(=O)C(Cl)=O.[CH3:19][C:20]1[C:24]([CH3:25])=[C:23]([NH:26][S:27]([C:30]2[C:31]([C:36]3[CH:41]=[CH:40][C:39]([C:42]4[O:43][CH:44]=[CH:45][N:46]=4)=[CH:38][C:37]=3[CH2:47][NH:48][CH3:49])=[CH:32][CH:33]=[CH:34][CH:35]=2)(=[O:29])=[O:28])[O:22][N:21]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH3:19][C:20]1[C:24]([CH3:25])=[C:23]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]2[CH:41]=[CH:40][C:39]([C:42]3[O:43][CH:44]=[CH:45][N:46]=3)=[CH:38][C:37]=2[CH2:47][N:48]([CH3:49])[C:3](=[O:5])[C:2]([CH3:1])([CH3:12])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)(=[O:29])=[O:28])[O:22][N:21]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 132222-Phenylisobutyric acidHCID 65578Oxalyl chlorideHCID 22103549HCID 22103549, compound

Product 1

HCID 22103508HCID 22103508, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To α,α-dimethylbenzeneacetic acid (16.4 mg, 0.1 mmol) and 0.003 ml DMF in 1 ml CH2Cl2, oxalyl chloride (2M in CH2 Cl2, 0.125 ml, 0.25 mmol) was added. The mixture was stirred at room temperature for 1 hr and 15 min and concentrated. The mixture, containing α,α-dimethylbenzeneacetyl chloride, was dissolved in 1 ml CH2Cl2 and cooled to 0° C., and N-(3,4-dimethyl-5-isoxazolyl)-2'-[(methylamino)methyl]-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (33 mg, 0.075 mmol, prepared as described in Step (A) of Example 28) and triethylamine (23 mg, 0.225 mmol) were added. The reaction was stirred at room temperature for 40 min and concentrated. The residue was purified by preparative HPLC on an ODS S10 column using 18% solvent A (10% MeOH, 90% H2O, 0.1% TFA) and 82% solvent B (90% MeOH, 10% H2O, 0.1% TFA) to provide the title compound of this Example (20 mg, 46%) as a white solid, m.p. 130°-138° C. (amorphous).

Workup

  1. concentrationconcentrated
  2. additionThe mixture, containing α,α-dimethylbenzeneacetyl chloride
  3. dissolutionwas dissolved in 1 ml CH2Cl2
  4. temperaturecooled to 0° C.
  5. stirringThe reaction was stirred at room temperature for 40 min
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC on an ODS S10 column

Sources & evidence

ORD record
ord-e2b8ccddc82449c59a5cb29ee30a4f33
Source dataset
uspto-grants-1998_12
Patent number
US05846990

Reaction notes

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