Water → 2-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 244697Notes

Reaction equation

HRID 244697 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([NH2:28])[C:13]4[CH:14]=[N:15][N:16]([S:19]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)(=[O:21])=[O:20])[C:17]=4[CH:18]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CCN(C(C)C)C(C)C.[Cl:38][CH2:39][C:40]1[S:41][CH:42]=[C:43]([C:45](Cl)=[O:46])[N:44]=1.O>C(Cl)(Cl)Cl>[Cl:38][CH2:39][C:40]1[S:41][CH:42]=[C:43]([C:45]([NH:28][C:12]2[CH:11]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[CH:3]=[CH:2][NH:1]4)[CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3[S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(=[O:21])=[O:20])=[O:46])[N:44]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 582680186-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amineHCID 597024562-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride2×

Product 1

HCID 583563582-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideYield 75.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
0 °C

Procedure

To solution of 6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine (1.5 g, 3.86 mmol) in chloroform (20 ml) at 0° C. was added DIPEA (1.35 ml, 7.72 mmol). 2-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.8 g, 6.98 mmol) in chloroform (20 ml) was added dropwise and the mixture was stirred at 0° C. for 1 h 15 mins. The mixture was allowed to warm to room temperature and stirring continued for 18 h. A further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (0.2 g, 1.02 mmol) was added to the mixture which was stirred at room temperature for 30 mins. Water (50 ml) was added to quench the reaction and the mixture was extracted with DCM (2×100 ml), separating the layers using a hydrophobic frit. The organics were collected and solvent removed in vacuo to give a brown solid which was triturated with ether (10 ml). The solid was filtered off and dried in a vacuum oven overnight to afford the title compound (1.6 g).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirring
  3. waitcontinued for 18 h
  4. stirringwas stirred at room temperature for 30 mins
  5. customto quench
  6. customthe reaction
  7. extractionthe mixture was extracted with DCM (2×100 ml)
  8. customseparating the layers
  9. customThe organics were collected
  10. customsolvent removed in vacuo
  11. customto give a brown solid which
  12. customwas triturated with ether (10 ml)
  13. filtrationThe solid was filtered off
  14. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-7284d3b6ef9a4bcbafa4616bbda56ee6
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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