Water → 6-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-yl}-2-pyridinecarboxamide

HRID 1615995Notes

Reaction equation

HRID 1615995 reaction equation
[Cl:1][CH2:2][C:3]1[N:8]=[C:7]([C:9](Cl)=[O:10])[CH:6]=[CH:5][CH:4]=1.[C:12]1([S:18]([N:21]2[C:29]3[CH:28]=[C:27]([C:30]4[CH:31]=[C:32]5[CH:38]=[N:37][N:36]([S:39]([C:42]6[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=6)(=[O:41])=[O:40])[C:33]5=[N:34][CH:35]=4)[CH:26]=[C:25]([NH2:48])[C:24]=3[CH:23]=[N:22]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C.O>C(Cl)(Cl)Cl>[Cl:1][CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:48][C:25]2[CH:26]=[C:27]([C:30]3[CH:31]=[C:32]4[CH:38]=[N:37][N:36]([S:39]([C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)(=[O:41])=[O:40])[C:33]4=[N:34][CH:35]=3)[CH:28]=[C:29]3[C:24]=2[CH:23]=[N:22][N:21]3[S:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:20])=[O:19])=[O:10])[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 58268026HCID 58268026, compoundHCID 866533026-(Chloromethyl)-2-pyridinecarbonyl chloride2×

Product 1

HCID 582680116-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-yl}-2-pyridinecarboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 6-(hydroxymethyl)-2-pyridinecarboxylic acid (500 mg, 3.27 mmol) in chloroform (10 ml) and N,N-dimethylformamide (DMF) (0.1 ml) was added thionyl chloride (1 ml, 13.70 mmol) and the mixture heated at 65° C. for 1 hr. Solvent was removed in vacuo and the residue was azeotroped with chloroform (5 ml) then dried on a high vacuum line for 30 mins to afford an orange oil (650 mg), presumed to be 6-(chloromethyl)-2-pyridinecarbonyl chloride. To solution of 1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-amine (581 mg, 1.095 mmol) in chloroform (5 ml) at 0° C. was added DIPEA (0.383 ml, 2.190 mmol). 6-(chloromethyl)-2-pyridinecarbonyl chloride (330 mg, 1.737 mmol) in chloroform (5 ml) was added dropwise and the mixture was stirred at 0° C. for 15 min then allowed to warm to room temperature and stirred for another 30 mins. Water (10 ml) was added to quench the reaction and the mixture was extracted with DCM (2×20 ml), separating the layers using a hydrophobic frit. The solvent was removed in vacuo to give a brown solid, which was triturated with ether (5 ml). The resultant cream solid was filtered off and dried in a vacuum oven for 30 mins to afford the title compound (658 mg).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for another 30 mins
  3. customto quench
  4. customthe reaction
  5. extractionthe mixture was extracted with DCM (2×20 ml)
  6. customseparating the layers
  7. customThe solvent was removed in vacuo
  8. customto give a brown solid, which
  9. customwas triturated with ether (5 ml)
  10. filtrationThe resultant cream solid was filtered off
  11. customdried in a vacuum oven for 30 mins

Sources & evidence

ORD record
ord-0ae58cb8947340dc87a2fc2e138afe9b
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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