Oxalyl chloride → N-(5-(3,5-Difluorobenzoyl)-1-trityl-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-nitrobenzamide

HRID 512938Notes

Reaction equation

HRID 512938 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=2)[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.[NH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:37]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=3)=[O:38])[CH:35]=2)[N:30]([C:47]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[N:29]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.CN(C)C=O>[F:46][C:41]1[CH:40]=[C:39]([CH:44]=[C:43]([F:45])[CH:42]=1)[C:37]([C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:47]([C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)[N:29]=[C:28]2[NH:27][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:9]([N:6]2[CH2:5][CH2:4][N:3]([CH3:2])[CH2:8][CH2:7]2)=[CH:10][C:11]=1[N+:18]([O-:20])=[O:19])=[O:38]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 667368904-(4-Methylpiperazin-1-yl)-2-nitrobenzoic acid hydrochlorideHCID 68670918(3-amino-1-trityl-1H-indazol-5-yl)(3,5-difluorophenyl)methanone

Product 1

HCID 68671004N-(5-(3,5-Difluorobenzoyl)-1-trityl-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-nitrobenzamideYield 92.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 4-(4-methyl-piperazin-1-yl)-2-nitro-benzoic acid hydrochloride (1.5 g, 4.97 mmol) in dry tetrahydrofuran (80 mL) were added oxalyl chloride (1.4 mL, 19.9 mmol) and N,N-dimethylformamide (1-2 drops). The mixture was stirred at room temperature overnight and then evaporated to dryness. The resulting crude acyl chloride was taken-up with toluene and evaporated again then dissolved in dry tetrahydrofuran (180 mL). A solution of (3-amino-1-trityl-1H-indazol-5-yl)-(3,5-difluoro-phenyl)-methanone (1.83 g. 3.55 mmol) and N,N-diisopropylethylamine (2.5 mL, 14.22 mmol) in dry tetrahydrofuran (15 mL) was added to the reaction mixture. The mixture was stirred at room temperature overnight and then at 75° C. for 2 hours. The volatiles were evaporated and the residue taken up with dichloromethane and washed with brine. The organic phase was dried over sodium sulfate and evaporated to dryness. Purification of the crude by chromatography over silica gel (DCM/MeOH) afforded 2.51 g of the title compound as yellow powder (92% yield).

Workup

  1. customevaporated to dryness
  2. customevaporated again
  3. dissolutionthen dissolved in dry tetrahydrofuran (180 mL)
  4. stirringThe mixture was stirred at room temperature overnight
  5. waitat 75° C. for 2 hours
  6. customThe volatiles were evaporated
  7. washwashed with brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. customevaporated to dryness
  10. customPurification of the crude by chromatography over silica gel (DCM/MeOH)

Sources & evidence

ORD record
ord-5a9ec05505614cb8997440a857a3d649
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Reaction notes

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