1,2-Dichloroethane → 1-(cyclopropanecarbonyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

HRID 336810Notes

Reaction equation

HRID 336810 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]([NH:22][S:23]([C:26]3[CH:27]=[C:28]([NH:32][C:33]([CH:35]4[CH2:38][NH:37][CH2:36]4)=[O:34])[CH:29]=[CH:30][CH:31]=3)(=[O:25])=[O:24])=[N:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(O[BH-](O[C:49](=[O:51])[CH3:50])OC(=O)C)(=O)C.C[N+](C)(C)C.Cl[CH2:58][CH2:59]Cl>CN(C=O)C>[CH:50]1([C:49]([N:37]2[CH2:38][CH:35]([C:33]([NH:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([S:23](=[O:25])(=[O:24])[NH:22][C:13]4[C:12]([NH:11][C:5]5[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=5)=[N:21][C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]=4)[CH:27]=3)=[O:34])[CH2:36]2)=[O:51])[CH2:59][CH2:58]1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 13696215Tetramethylammonium Triacetoxyborohydride (>90%)HCID 57448472N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

Product 1

HCID 574485091-(cyclopropanecarbonyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide (110 mg, 0.19 mmol), prepared using procedures similar to those described in Example 372, in 3 mL of DCE and 200 μL of DMF, aldehyde (0.77 mmol, 4.0 eq.) was added slowly followed by tetramethylammonium triacetoxyborohydride (1.16 mmol, 6.0 eq). The reaction was stirred at room temperature overnight. LC/MS indicated the reaction was completed. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH4OAc/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.

Workup

  1. customThe solvent was subsequently removed under reduced pressure on a rotary evaporator
  2. dissolutionThe crude material was then redissolved in methanol
  3. customPurification of the final product
  4. customequipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column
  5. customthe purification

Sources & evidence

ORD record
ord-319ee1d232e04b70ab9c38f35a7b59a2
Source dataset
uspto-grants-2014_11
Patent number
US08889664B2

Reaction notes

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