Water → HCID 57848858, compound

HRID 736265Notes

Reaction equation

HRID 736265 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:18]=[CH:17][C:13]([C:14](Cl)=[O:15])=[CH:12][CH:11]=2)[CH2:5][CH2:4]1.[NH2:19][C:20]1[C:21]2[CH:34]=[C:33]([C:35]([NH:37][N:38]([CH3:45])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[O:36])[S:32][C:22]=2[N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[N:24]=1.CN1CCN(CC2C=CC(C(Cl)=O)=CC=2)CC1.O>N1C=CC=CC=1>[CH3:45][N:38]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[NH:37][C:35]([C:33]1[S:32][C:22]2[N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[N:24]=[C:20]([NH:19][C:14](=[O:15])[C:13]3[CH:17]=[CH:18][C:10]([CH2:9][N:6]4[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]4)=[CH:11][CH:12]=3)[C:21]=2[CH:34]=1)=[O:36]

Participants

6

Reactant 4

HCID 962WaterHCID 137489624-[(4-Methylpiperazin-1-yl)methyl]benzoyl chlorideHCID 57848800HCID 57848800, compoundHCID 87384739106261-64-7

Product 1

HCID 57848858HCID 57848858, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

391 mg (1.55 mmol) of 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride hydrochloride are added to a solution of 0.30 g (0.77 mmol) of tert-butyl 3-amino-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate in 16 mL of pyridine under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 16 hours, a further 294 mg (1.16 mmol) of 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride are then added and stirring is continued for 5 hours. The reaction mixture is then cooled to a temperature in the region of 10° C. and then treated with 50 mL of water. The mixture is extracted twice with 100 mL of ethyl acetate. The organic phases are combined, washed with water to neutral pH, dried over magnesium sulfate, filtered and then concentrated to dryness under vacuum (3 kPa) at a temperature in the region of 30° C. The residue is purified by chromatography on a cartridge of 25 g of silica gel (0.015-0.040 mm), eluting successively with dichloromethane/methanol mixtures (98/2 by volume, and then 97/3, then 96/4 and finally 95/5) at a flow rate of 15 mL/min. The fractions containing the expected product are combined and then concentrated to dryness under reduced pressure (3 kPa) at a temperature in the region of 30° C. 0.14 g of tert-butyl 5-(N′-methyl-N′-phenylhydrazinocarbonyl)-3-[4-(4-methylpiperazin-1-ylmethyl)benzoylamino]thieno[2,3-c]pyrazole-1-carboxylate is thus obtained in the form of an off-white solid melting at 218° C. tert-Butyl 3-amino-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate is described in example 8. 4-(4-Methylpiperazin-1-ylmethyl)benzoyl chloride may be prepared according to patent WO 03/066 613 A1.

Workup

  1. stirringstirring
  2. waitis continued for 5 hours
  3. temperatureThe reaction mixture is then cooled to a temperature in the region of 10° C.
  4. extractionThe mixture is extracted twice with 100 mL of ethyl acetate
  5. washwashed with water to neutral pH
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under vacuum (3 kPa) at a temperature in the region of 30° C
  9. customThe residue is purified by chromatography on a cartridge of 25 g of silica gel (0.015-0.040 mm)
  10. washeluting successively with dichloromethane/methanol mixtures (98/2 by volume
  11. additionThe fractions containing the expected product
  12. concentrationconcentrated to dryness under reduced pressure (3 kPa) at a temperature in the region of 30° C

Sources & evidence

ORD record
ord-3714e9ad843148cb97e11da27542ebb7
Source dataset
uspto-grants-2009_09
Patent number
US07595320B2

Reaction notes

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