3-Chloropropanesulphonyl chloride → HCID 131730787, compound

HRID 80937Notes

Reaction equation

HRID 80937 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[N:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=3)=[CH:12][N:11]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[Cl:23][CH2:24][CH2:25][CH2:26][S:27](Cl)(=[O:29])=[O:28].[H-].[Na+]>CN(C=O)C>[ClH:23].[ClH:23].[O:28]=[S:27]1(=[O:29])[CH2:26][CH2:25][CH2:24][N:22]1[C:19]1[CH:20]=[CH:21][C:16]([C:13]2[N:14]=[CH:15][C:10]([N:7]3[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]3)=[N:11][CH:12]=2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 154103-Chloropropanesulphonyl chlorideHCID 24758Sodium hydrideHCID 671451114-(4-Isopropyl-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl-5'-yl)phenylamine

Product 1

HCID 131730787HCID 131730787, compoundYield 46.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(4-isopropyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-yl)phenylamine (0.34 g, 1.14 mmol), 3-chloro-1-propanesulfonyl chloride (0.20 g, 1.14 mmol) and TEA (0.12 g, 1.14 mmol) in DMF was stirred at rt for 1 h. NaH (0.055 g, 2.29 mmol) was added and stirring was continued for 5 h. The reaction mixture was transferred to a microwave vial (20 mL) and heated for 1000 s at 80° C. in a microwave oven. The reaction mixture was evaporated in vacuo and redissolved in a mixture of DCM and water. The phases were separated and the aqueous phase was extracted with DCM (2×25 mL). The combined organic extracts were evaporated in vacuo, redissolved in MeOH and purified by preparative HPLC Method B. This afforded 220 mg of a solid which was redissolved in MeOH and treated with HCl in diethyl ether. The volatiles were evaporated to give 126 mg (22%) of the title compound.

Workup

  1. stirringstirring
  2. waitwas continued for 5 h
  3. temperatureheated for 1000 s at 80° C. in a microwave oven
  4. customThe reaction mixture was evaporated in vacuo
  5. dissolutionredissolved in a mixture of DCM and water
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with DCM (2×25 mL)
  8. customThe combined organic extracts were evaporated in vacuo
  9. dissolutionredissolved in MeOH
  10. custompurified by preparative HPLC Method B
  11. dissolutionThis afforded 220 mg of a solid which was redissolved in MeOH
  12. additiontreated with HCl in diethyl ether
  13. customThe volatiles were evaporated

Sources & evidence

ORD record
ord-97e67e081480466ebf7bd3ac93f4dfd6
Source dataset
uspto-grants-2014_09
Patent number
US08846677B2

Reaction notes

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