Hydrochloric Acid → HCID 178496512, compound

HRID 538409Notes

Reaction equation

HRID 538409 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:25]([CH3:28])([CH3:27])[CH3:26])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17]C(=O)OC(C)(C)C)[CH3:16])[N:8]=1.Cl.C(N(C(C)C)CC)(C)C.[CH3:39][O:40][CH2:41][C:42](Cl)=[O:43]>CO.C(Cl)Cl>[Br:1][C:2]1[N:3]=[C:4]([C:25]([CH3:27])([CH3:28])[CH3:26])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17][C:42](=[O:43])[CH2:41][O:40][CH3:39])[CH3:16])[N:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 178461767(S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

Product 1

HCID 178496512HCID 178496512, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (2.6 g, 4.4 mmol) in methanol was treated with aqueous 12 N HCl (1.4 mL. 16.8 mmol). The reaction was heated at 60° C. for 1 h, and allowed to cool to rt. The reaction was then concentrated and dried in vacuo to give 1.6 g of a crude residue which was carried forward without further purification. The residue was treated with diisopropylethyl amine (4.6 mL, 26.3 mmol) in dry DCM (18 mL), followed by the dropwise addition of methoxyacetyl chloride (0.44 mL, 4.8 mmol). The reaction mixture was stirred at rt for 1 h, then concentrated, in vacuo, to dryness. The remaining residue was dissolved in EtOAc (40 mL) was washed with water (2×), dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography (SiO2, 90:10-50:50 hexanes-EtOAc) to afford 1.3 g of (S)—N-(1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-yl)-2-methoxyacetamide:

Workup

  1. temperatureto cool to rt
  2. concentrationThe reaction was then concentrated
  3. customdried in vacuo
  4. customto give 1.6 g of a crude residue which
  5. customwas carried forward without further purification
  6. concentrationconcentrated, in vacuo, to dryness
  7. dissolutionThe remaining residue was dissolved in EtOAc (40 mL)
  8. washwas washed with water (2×)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe crude residue was purified by flash chromatography (SiO2, 90:10-50:50 hexanes-EtOAc)

Sources & evidence

ORD record
ord-94baaa4a0af54ec1b7d164a80d2f2756
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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