Ethanesulfonylchloride, 2-chloro- → Tak-653

HRID 1405841Notes

Reaction equation

HRID 1405841 reaction equation
[H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[CH:10]1([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:24]([NH2:30])=[N:25][CH:26]=[C:27]([CH3:29])[N:28]=3)=[CH:19][CH:18]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1>C1COCC1>[CH:10]1([O:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[C:24]4=[N:30][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:25]4[CH:26]=[C:27]([CH3:29])[N:28]=3)=[CH:21][CH:22]=2)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 24758Sodium hydrideHCID 667484133-(4-(Cyclohexyloxy)phenyl)-5-methylpyrazin-2-amine

Product 1

HCID 56655833Tak-653

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (60%, 5.29 g) in THF (dry) (100 mL) was added 2-chloroethanesulfonyl chloride (5.57 mL) at 0° C. and the mixture was stirred for 10 min at the same temperature. A solution of 3-(4-(cyclohexyloxy)phenyl)-5-methylpyrazin-2-amine (7.5 g) in THF (dry) (75 mL) was added at 0° C. and the mixture was stirred at room temperature under nitrogen for 2 days. The mixture was quenched with water/THF at 0° C. carefully and water was added to form precipitates which were washed with EtOAc and water and dried in vacuo to give crude title compound (4.7 g). The part of this material (ca. 4.3 g) was crystallized from DMSO (200 mL)-EtOH (40 mL)/water (400 mL) to give 9-[4-(cyclohexyloxy)phenyl]-7-methyl-3,4-dihydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide as light-yellow crystals (3.6 g), which was recrystallized from DMSO (100 mL)-EtOH (15 mL)/water (100 mL) at 80° C. to room temperature to give the title compound (3.09 g) as light-yellow crystals.

Workup

  1. stirringthe mixture was stirred at room temperature under nitrogen for 2 days
  2. customThe mixture was quenched with water/THF at 0° C. carefully
  3. additionwater was added
  4. customto form
  5. customprecipitates which
  6. washwere washed with EtOAc and water
  7. customdried in vacuo
  8. customto give crude title compound (4.7 g)
  9. customThe part of this material (ca. 4.3 g) was crystallized from DMSO (200 mL)-EtOH (40 mL)/water (400 mL)

Sources & evidence

ORD record
ord-f5465c32ddb24dce959bd04d1590c41a
Source dataset
uspto-grants-2014_12
Patent number
US08916551B2

Reaction notes

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