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

HRID 1907854Notes

Reaction equation

HRID 1907854 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) δppm 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-489ac44f4d3c40fb93aab97ba4363f6f
Source dataset
uspto-grants-2013_12
Patent number
US08598186B2

Reaction notes

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