Triethylamine → (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutan-1-ol

HRID 1055041Notes

Reaction equation

HRID 1055041 reaction equation
[NH2:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4].[Cl:9][C:10]1[N:15]=[C:14](Cl)[C:13]([F:17])=[CH:12][N:11]=1.C(N(CC)CC)C.[NH4+].[Cl-]>CN(C=O)C>[Cl:9][C:10]1[N:15]=[C:14]([NH:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4])[C:13]([F:17])=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 2734079(2S)-2-Amino-3,3-dimethyl-1-butanol

Product 1

HCID 86714732(S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutan-1-olYield 63.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (2S)-2-amino-3,3-dimethyl-butan-1-ol (5.0 g, 42.7 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (5.7 g, 42.7 mmol) in DMF (50 mL) was added triethylamine (7.1 mL, 51.2 mmol). After 90 minutes, the reaction was diluted into aqueous saturated NH4Cl solution and extracted twice with EtOAc. The combined organic phases were washed twice with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-10% MeOH/CH2Cl2 gradient) to afford 6.7 g of the desired product, 1, as a sticky solid: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=2.48 minutes (M+H) 248.32.

Workup

  1. extractionextracted twice with EtOAc
  2. washThe combined organic phases were washed twice with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (0-10% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-8ec5419a5a3c468d8de4f303281bf40e
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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