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

HRID 513150Notes

Reaction equation

HRID 513150 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-de4d729f0f7349f4ae24dcc2393d9b08
Source dataset
uspto-grants-2015_08
Patent number
US09102682B2

Reaction notes

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