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

HRID 2171836Notes

Reaction equation

HRID 2171836 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-cc137e17a2ba4338add3b2521d45d2e9
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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