Hydrochloric Acid → 2-Amino-6-(4-(tert-butoxycarbonylamino)-butanoylamino)-5-nitroso-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidine

HRID 1695091Notes

Reaction equation

HRID 1695091 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C(OC(Cl)=O)C(C)C.[NH2:32][C:33]1[N:38]=[C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([CH2:47][NH:48][C:49](=[O:54])[C:50]([F:53])([F:52])[F:51])=[CH:43][CH:42]=2)[C:36]([N:55]=[O:56])=[C:35]([NH2:57])[N:34]=1.Cl>C1COCC1>[NH2:32][C:33]1[N:38]=[C:37]([O:39][CH2:40][C:41]2[CH:42]=[CH:43][C:44]([CH2:47][NH:48][C:49](=[O:54])[C:50]([F:52])([F:53])[F:51])=[CH:45][CH:46]=2)[C:36]([N:55]=[O:56])=[C:35]([NH:57][C:12](=[O:14])[CH2:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[N:34]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 62365Isobutyl chloroformateHCID 81531DiisopropylethylamineHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 86615611HCID 86615611, compound

Product 1

HCID 866156122-Amino-6-(4-(tert-butoxycarbonylamino)-butanoylamino)-5-nitroso-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidineYield 50.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere 4-(tert-butoxycarbonylamino)-butyric acid (1.58 g, 8 mmol) is dissolved in 20 mL dry THF and cooled to 0° C. Diisopropyl ethylamine (1.18 g, 9 mmol) is added, the mixture cooled to −20° C., and chloroformic acid isobutylester (1.15 g, 8 mmol) added. The mixture is stirred at this temperature for 5 min, and nitroso-pyrimidine 38 (Example 21, 2.64 g, 7 mmol) dissolved in 20 mL dry THF is added via a syringe. The reaction mixture is allowed to warm to room temperature, heated to 55° C. and stirred at this temperature over night. After cooling to room temperature, the mixture is poured into 100 mL of 1 N HCl and the product extracted with ethyl acetate (300 mL). The combined organic phases are washed with water and brine, subsequently dried over MgSO4 and the solvent evaporated. The residue is adsorbed on SiO2 and purified by flash column chromatography (cyclohexane/ethyl acetate 1:2 to 1:10) to yield the title compound as a blue solid (1.96 g, 3.53 mmol, 50.4%). From the crude material, an analytical sample is recrystallized from ethyl acetate.

Workup

  1. temperaturethe mixture cooled to −20° C.
  2. additionis added via a syringe
  3. temperatureto warm to room temperature
  4. temperatureheated to 55° C.
  5. stirringstirred at this temperature over night
  6. temperatureAfter cooling to room temperature
  7. extractionthe product extracted with ethyl acetate (300 mL)
  8. washThe combined organic phases are washed with water and brine
  9. dry with materialsubsequently dried over MgSO4
  10. customthe solvent evaporated
  11. custompurified by flash column chromatography (cyclohexane/ethyl acetate 1:2 to 1:10)

Sources & evidence

ORD record
ord-9e74887465514fbcb8adb6b63bd7bd7a
Source dataset
uspto-grants-2012_04
Patent number
US08163479B2

Reaction notes

Loading…