Diisopropylethylamine → tert-butyl N-[2-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]-3-methyl-butyl]carbamate

HRID 72783Notes

Reaction equation

HRID 72783 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[NH2:19][CH:20]([CH:30]([CH3:32])[CH3:31])[CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26]>C(O)C>[Br:1][C:2]1[C:3]([NH:19][CH:20]([CH:30]([CH3:32])[CH3:31])[CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2899735-Bromo-2,4-dichloropyrimidineHCID 71437538tert-butyl N-(2-amino-3-methylbutyl)carbamate

Product 1

HCID 86695593tert-butyl N-[2-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]-3-methyl-butyl]carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 5-bromo-2,4-dichloro-pyrimidine 7.11 g (0.0312 mole) in ethanol (100 mL) was added diisopropylethyl amine 5.45 mL (1.0 eq) and tert-butyl N-(2-amino-3-methyl-butyl)carbamate 6.31 g (0.0312 mole). The reaction mixture was stirred at room temperature for 20 hrs. After concentration under vacuum, ethyl acetate and water was added. The organic layer was separated, dried with magnesium sulfate and then concentrated under vacuum. The crude product was purified by column chromatography using hexane/ethyl acetate (0-30%) over silica gel to afford tert-butyl N-[2-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]-3-methyl-butyl]carbamate. 1H NMR (600 MHz, DMSO-d6) δ ppm 0.77-0.85 (d, J=6.5 Hz, 3H) 0.87 (d, J=6.73 Hz, 3H) 1.31-1.39 (m, 9H) 1.82-1.93 (m, 1H) 2.94 (d, J=5.56 Hz, 1H) 3.08-3.22 (m, 2H) 3.98 (d, J=8.20 Hz, 1H) 6.96 (d, J=8.78 Hz, 1H) 8.21 (s, 1H). LCMS (ESI) 393 (M+H).

Workup

  1. concentrationAfter concentration under vacuum, ethyl acetate and water
  2. additionwas added
  3. customThe organic layer was separated
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-a153c96adf934987a9e31d62c9ffc804
Source dataset
uspto-grants-2014_09
Patent number
US08829012B2

Reaction notes

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