Hydrochloric Acid → (RS)-S-[4-({5-bromo-4-[(R)-(2-hydroxy-1,2-dimethylpropyl)amino]-pyrimidin-2-yl}amino)phenyl]-S-cyclopropyl-N-[2-(trimethylsilyl)ethylsulfonyl]-sulfoximide

HRID 1391438Notes

Reaction equation

HRID 1391438 reaction equation
[Br:1][C:2]1[C:3]([NH:9][C@H:10]([CH3:15])[C:11]([CH3:14])([OH:13])[CH3:12])=[N:4][C:5](Cl)=[N:6][CH:7]=1.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([CH:35]2[CH2:37][CH2:36]2)(=[N:25][S:26]([CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])(=[O:28])=[O:27])=[O:24])=[CH:19][CH:18]=1.Cl>C(#N)C.O1CCOCC1.O>[Br:1][C:2]1[C:3]([NH:9][C@H:10]([CH3:15])[C:11]([OH:13])([CH3:14])[CH3:12])=[N:4][C:5]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:35]3[CH2:37][CH2:36]3)(=[N:25][S:26]([CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])(=[O:27])=[O:28])=[O:24])=[CH:19][CH:18]=2)=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 59674068(R)-3-(5-bromo-2-chloropyrimidin-4-ylamino)-2-methylbutan-2-olHCID 59674073(RS)-S-(4-aminophenyl)-S-cyclopropyl-N-[2-(trimethylsilyl)ethylsulfonyl]sulfoximide

Product 1

HCID 59674047(RS)-S-[4-({5-bromo-4-[(R)-(2-hydroxy-1,2-dimethylpropyl)amino]-pyrimidin-2-yl}amino)phenyl]-S-cyclopropyl-N-[2-(trimethylsilyl)ethylsulfonyl]-sulfoximide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

95 mg (0.32 mmol) of (R)-3-[(5-bromo-2-chloropyrimidin-4-yl)amino]-2-methyl-butan-2-ol is dissolved in 2 ml of acetonitrile and mixed with 116 mg (0.32 mmol) of (RS)-S-(4-aminophenyl)-S-cyclopropyl-N-[2-(trimethylsilyl)ethylsulfonyl]sulfoximide. After 0.08 ml of an approximately 4N solution of HCl in dioxane and 0.08 ml of water are added, the mixture is heated in a sealed vessel for 16 hours to 75° C. The suspension is filtered, and the filtrate is separated by flash chromatography (dichloromethane-dichloromethane/ethanol 95:5, 15 ml/min). The fractions, 43-51 min, contain 50 mg (25% of theory) of the desired product.

Workup

  1. temperaturethe mixture is heated in a sealed vessel for 16 hours to 75° C
  2. filtrationThe suspension is filtered
  3. customthe filtrate is separated by flash chromatography (dichloromethane-dichloromethane/ethanol 95:5, 15 ml/min)
  4. customThe fractions, 43-51 min

Sources & evidence

ORD record
ord-28e6a224a52f4a4e8c23255b08e48d2d
Source dataset
uspto-grants-2008_03
Patent number
US07338958B2

Reaction notes

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