Potassium Carbonate → (S)-tert-Butyl 2-(2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethyl-butylthio)ethanoate

HRID 1055129Notes

Reaction equation

HRID 1055129 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:10][SH:11])[C:5]([F:16])=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>CC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:13])([CH3:15])[CH3:14])[CH2:10][S:11][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:5]([F:16])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 86714752(S)-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutane-1-thiol2×

Product 1

HCID 86714775(S)-tert-Butyl 2-(2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethyl-butylthio)ethanoate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirring suspension of (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutane-1-thiol, 77a, (1.50 g, 5.69 mmol) and K2CO3 (2.36 g, 17.06 mmol) in acetone (15 mL) was added tert-butyl bromoacetate (1.26 mL, 8.53 mmol). The suspension was stirred at room temperature for 18 hours. The resulting solid was filtered, washed with acetone and the filtrate was concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0-30% EtOAc/Hexanes gradient) to afford 1.6 g of the desired product as an off-white solid: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.81 minutes (M+H) 378.06.

Workup

  1. filtrationThe resulting solid was filtered
  2. washwashed with acetone
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe crude residue was purified by silica gel chromatography (0-30% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-84b2667bf713490fba43efd373d0ca9e
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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