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

HRID 520580Notes

Reaction equation

HRID 520580 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-carboxamide

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) in chloroform (20 ml) at 0° C. was added DIPEA (1.35 ml). 2-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.8 g) in chloroform (20 ml) was added dropwise and the mixture was stirred at 0° C. for 1 h 15 min. The mixture was allowed to warm to RT and stirring continued for 18 h. A further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (0.2 g) was added to the mixture which was stirred at RT for 30 min. Water (50 ml) was added 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 and dried in a vacuum oven overnight to afford the title compound, 1.6 g.

Workup

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

Sources & evidence

ORD record
ord-2ba7b841f0b04b6e8281bfb97422a69c
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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