Trichloroacetyl isocyanate → tert-Butyl (E)-3-(2-{3-[(aminocarbonyl)oxy]piperidino}-8-{[(4-cyclobutyl-1,3-thiazol-2-yl)amino]carbonyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoate

HRID 1828460Notes

Reaction equation

HRID 1828460 reaction equation
[CH:1]1([C:5]2[N:6]=[C:7]([NH:10][C:11]([C:13]3[CH:39]=[CH:38][N:16]4[C:17](=[O:37])[C:18](/[CH:28]=[CH:29]/[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[C:19]([N:21]5[CH2:26][CH2:25][CH2:24][CH:23]([OH:27])[CH2:22]5)[N:20]=[C:15]4[CH:14]=3)=[O:12])[S:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.ClC(Cl)(Cl)[C:42]([N:44]=C=O)=[O:43]>C(OCC)(=O)C>[NH2:44][C:42]([O:27][CH:23]1[CH2:24][CH2:25][CH2:26][N:21]([C:19]2[N:20]=[C:15]3[CH:14]=[C:13]([C:11]([NH:10][C:7]4[S:8][CH:9]=[C:5]([CH:1]5[CH2:4][CH2:3][CH2:2]5)[N:6]=4)=[O:12])[CH:39]=[CH:38][N:16]3[C:17](=[O:37])[C:18]=2/[CH:28]=[CH:29]/[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:22]1)=[O:43]

Participants

4

Reactant 2

HCID 76400Trichloroacetyl isocyanate2×HCID 86588105tert-Butyl (E)-3-[8-{[(4-cyclobutyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(3-hydroxy-piperidino)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl]-2-propenoate

Product 1

HCID 86588106tert-Butyl (E)-3-(2-{3-[(aminocarbonyl)oxy]piperidino}-8-{[(4-cyclobutyl-1,3-thiazol-2-yl)amino]carbonyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl (E)-3-[8-{[(4-cyclobutyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(3-hydroxypiperidino)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl]-2-propenoate (16 mg, 0.029 mmol) was dissolved in ethyl acetate (3 ml), added with trichloroacetyl isocyanate (10 μl) under ice cooling, stirred at 0° C. for 1 hour, then further added with trichloroacetyl isocyanate (10 μl), and further stirred for 30 minutes. Then, the reaction solution was concentrated under reduced pressure, and the resulting residue was added with methanol (2 ml), water (0.2 ml) and sodium formate (12 mg) at room temperature and stirred at room temperature for 7 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by thin layer silica gel chromatography (chloroform:methanol=30:1) to obtain 20 mg of the title compound.

Workup

  1. stirringfurther stirred for 30 minutes
  2. concentrationThen, the reaction solution was concentrated under reduced pressure
  3. additionthe resulting residue was added with methanol (2 ml), water (0.2 ml) and sodium formate (12 mg) at room temperature
  4. stirringstirred at room temperature for 7 hours
  5. concentrationThe reaction solution was concentrated under reduced pressure
  6. customthe residue was purified by thin layer silica gel chromatography (chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-802f8a732c5f4369bc9a37d74c3efe70
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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